FoxO1调控猪骨骼肌纤维类型转化的初步研究
摘要
骨骼肌纤维类型根据其形态、功能和生理生化特性分为Ⅰ型和Ⅱ型,提高Ⅰ型肌纤维的比例是改善畜禽肉品质的主要途径。长期以来,国内外许多学者致力于通过功能基因调控肌纤维类型来改善畜禽肉品质。近年来研究表明,叉头转录因子O亚家族1(forkhead transcription factor group o1,FoxO1)可能是骨骼肌成肌细胞分化过程的重要调控因子,其通过多条通路在调控骨骼肌成肌细胞的增殖与分化中发挥重要作用。因此,本试验以猪为模式动物,利用细胞培养,sq RT-PCR,Western Blot,RNA干扰等细胞生物学和分子生物学技术,研究FoxO1在猪骨骼肌纤维类型发育过程中的调控作用。获得如下结果:
1.在SOL、LD、EDL和GAST这四种类型骨骼肌中,mRNA水平检测发现,MyHCⅠ和MyHCⅡa的表达量在SOL中较高,而MyHCⅡb和MyHCⅡx在SOL中表达量较低;在EDL和GAST中,MyHCⅡb和MyHCⅡx的表达量较高。FoxO1在SOL和GAST中表达较高,但在LD和EDL中表达较低,FoxO1在这四种类型骨骼肌中的表达量与Sirt1和NFAT相似,但与Mef2c相反。Western Blot显示:FoxO1蛋白在SOL中表达最低。表明FoxO1在不同类型骨骼肌中表达量有差异,与肌纤维类型相关基因密切相关。
2.体外培养诱导分化1~9d的骨骼肌成肌细胞发现,FoxO1基因mRNA的表达量变化不明显,但是其蛋白表达却随着细胞分化表达量逐渐上升,并且MyHCⅡb和MyHCⅡx的mRNA表达量也逐渐上升,与FoxO1蛋白表达趋势一致。表明在骨骼肌成肌细胞分化过程中,FoxO1与Ⅱ型肌纤维的表达相关。
3.采用50nM的渥曼青霉素处理猪成肌细胞0,3,5天,利用sq RT- PCR和Western Blot等技术,检测肌肉形成与肌纤维类型相关基因的表达。结果显示:激活内源活性FoxO1, MyHCⅡb、MyHCⅡx和NFAT表达显著上调,而MyHCⅠ、MyHCⅡa和Mef2c表达显著下调。所以FoxO1可能通过NFAT和Mef2c调控肌纤维类型。
4.根据RNAi引物设计原则,设计猪FoxO1基因shRNA的四条干扰引物序列,合成、退火形成双链寡核酸后克隆到慢病毒载体Lenti H1 vector的黏性末端,测序,初步成功连接FoxO1-shRNA慢病毒干扰载体,为进一步研究研究FoxO1基因在调节猪肌纤维类型转化过程中的作用机理奠定基础。
Based on the different structural, functional, physics and chemical properties, Skeletal muscle is composed of typeⅠ,Ⅱa ,Ⅱx andⅡb. Through improving the content of typeⅠm uscle, we could make meat quality better. For a long period of time, many scholars want to improve meat quality by controling the content of muscle fiber type. The studies in recent years showed that FoxO1 might be the key regulatory factor during process of myoblast differentiation. It may influence cell proliferation and differentiation through multiple ways, hinting that procine FoxO1 plays an important modulatory role during formation of myocyte. Thereby, our study use pigs as model animal through cell culture, sq RT-PCR, Western Blot, RNAi and other methods in order to clarify the role of FoxO1 in the regulation of development of muscle fiber type. The main reserch results as follows:
1. In the SOL, LD, EDL and GAST of skeletal muscle. RT-PCR detection showed the expression levels of MyHCⅠand MyHCⅡa were much higher, whereas the expression levels of MyHCⅡb and MyHCⅡx were much lower in SOL; In contrast, the expression levels of MyHCⅡb and MyHCⅡx were much higher in LD and EDL. The expression of FoxO1 were higher in SOL and GAST than in LD and EDL, in addition, the expression of FoxO1 in four types of skeletal muscle were similar to Sirt1 and NFAT, but opposite to Mef2c. Western Blot assay indicated FoxO1 protein is lowest in SOL. The results demonstrated that the expression of FoxO1 in four types of skeletal muscle were different, and closely related to muscle fiber type-related genes.
2. We successfully separate and culture pig myocyte as a ideal material to study muscle fiber type.Through inducing differatiation in in vitro, we discovered during first 1 to 9 days, the content of FoxO1 protein increasd significantly but not the RNA level, with the time increasing, the level of MyHCⅡb and MyHCⅡx increased as the same as the he content of FoxO1 protein expression, however the RNA level of MyHCⅠand MyHCⅡdidn’t change. It is suggested during the differiation of myocyte, FoxO1 have an impaction on muscle fiber by poste-transcription.
3. To study the role of the dephosphorylation of FoxO1 on muscle fiber type, we collected the skeletal muscle myoblast on the day0, day3 and day5 after being treated with Wortmannin. We detected the expression of FoxO1, skeletal muscle fiber type gene markers and genes involved in muscle fiber type regulation, such as MyHC I, MyHCⅡa, MyHCⅡb and MyHCⅡx, NFAT and Mef2c by RT-PCR and Western blot. Results: Activation of FoxO1 in porcine myoblast dramatically increased the expression of MyHCⅡb, MyHCⅡx and NFAT, while the expression of MyHCⅠ, MyHCⅡa and Mef2C decreased obviously. FoxO1 may regulate muscle fiber type through Mef2c and NFAT mediated pathway.
4. RNAi design based on,the principle of primer design porcine FoxO1 gene shRNA sequence, synthesis, annealing after the formation of double-stranded oligonucleotides cloned into the lentiviral vector of the sticky end of Lenti H1 vector, sequencing, build FoxO1 gene RNAi lentiviral vector, bjective To construct a lentiviral vector-mediated RNAi of FoxO1 gene and provide the basis for further experiments in muscle fiber types.
1.在SOL、LD、EDL和GAST这四种类型骨骼肌中,mRNA水平检测发现,MyHCⅠ和MyHCⅡa的表达量在SOL中较高,而MyHCⅡb和MyHCⅡx在SOL中表达量较低;在EDL和GAST中,MyHCⅡb和MyHCⅡx的表达量较高。FoxO1在SOL和GAST中表达较高,但在LD和EDL中表达较低,FoxO1在这四种类型骨骼肌中的表达量与Sirt1和NFAT相似,但与Mef2c相反。Western Blot显示:FoxO1蛋白在SOL中表达最低。表明FoxO1在不同类型骨骼肌中表达量有差异,与肌纤维类型相关基因密切相关。
2.体外培养诱导分化1~9d的骨骼肌成肌细胞发现,FoxO1基因mRNA的表达量变化不明显,但是其蛋白表达却随着细胞分化表达量逐渐上升,并且MyHCⅡb和MyHCⅡx的mRNA表达量也逐渐上升,与FoxO1蛋白表达趋势一致。表明在骨骼肌成肌细胞分化过程中,FoxO1与Ⅱ型肌纤维的表达相关。
3.采用50nM的渥曼青霉素处理猪成肌细胞0,3,5天,利用sq RT- PCR和Western Blot等技术,检测肌肉形成与肌纤维类型相关基因的表达。结果显示:激活内源活性FoxO1, MyHCⅡb、MyHCⅡx和NFAT表达显著上调,而MyHCⅠ、MyHCⅡa和Mef2c表达显著下调。所以FoxO1可能通过NFAT和Mef2c调控肌纤维类型。
4.根据RNAi引物设计原则,设计猪FoxO1基因shRNA的四条干扰引物序列,合成、退火形成双链寡核酸后克隆到慢病毒载体Lenti H1 vector的黏性末端,测序,初步成功连接FoxO1-shRNA慢病毒干扰载体,为进一步研究研究FoxO1基因在调节猪肌纤维类型转化过程中的作用机理奠定基础。
Based on the different structural, functional, physics and chemical properties, Skeletal muscle is composed of typeⅠ,Ⅱa ,Ⅱx andⅡb. Through improving the content of typeⅠm uscle, we could make meat quality better. For a long period of time, many scholars want to improve meat quality by controling the content of muscle fiber type. The studies in recent years showed that FoxO1 might be the key regulatory factor during process of myoblast differentiation. It may influence cell proliferation and differentiation through multiple ways, hinting that procine FoxO1 plays an important modulatory role during formation of myocyte. Thereby, our study use pigs as model animal through cell culture, sq RT-PCR, Western Blot, RNAi and other methods in order to clarify the role of FoxO1 in the regulation of development of muscle fiber type. The main reserch results as follows:
1. In the SOL, LD, EDL and GAST of skeletal muscle. RT-PCR detection showed the expression levels of MyHCⅠand MyHCⅡa were much higher, whereas the expression levels of MyHCⅡb and MyHCⅡx were much lower in SOL; In contrast, the expression levels of MyHCⅡb and MyHCⅡx were much higher in LD and EDL. The expression of FoxO1 were higher in SOL and GAST than in LD and EDL, in addition, the expression of FoxO1 in four types of skeletal muscle were similar to Sirt1 and NFAT, but opposite to Mef2c. Western Blot assay indicated FoxO1 protein is lowest in SOL. The results demonstrated that the expression of FoxO1 in four types of skeletal muscle were different, and closely related to muscle fiber type-related genes.
2. We successfully separate and culture pig myocyte as a ideal material to study muscle fiber type.Through inducing differatiation in in vitro, we discovered during first 1 to 9 days, the content of FoxO1 protein increasd significantly but not the RNA level, with the time increasing, the level of MyHCⅡb and MyHCⅡx increased as the same as the he content of FoxO1 protein expression, however the RNA level of MyHCⅠand MyHCⅡdidn’t change. It is suggested during the differiation of myocyte, FoxO1 have an impaction on muscle fiber by poste-transcription.
3. To study the role of the dephosphorylation of FoxO1 on muscle fiber type, we collected the skeletal muscle myoblast on the day0, day3 and day5 after being treated with Wortmannin. We detected the expression of FoxO1, skeletal muscle fiber type gene markers and genes involved in muscle fiber type regulation, such as MyHC I, MyHCⅡa, MyHCⅡb and MyHCⅡx, NFAT and Mef2c by RT-PCR and Western blot. Results: Activation of FoxO1 in porcine myoblast dramatically increased the expression of MyHCⅡb, MyHCⅡx and NFAT, while the expression of MyHCⅠ, MyHCⅡa and Mef2C decreased obviously. FoxO1 may regulate muscle fiber type through Mef2c and NFAT mediated pathway.
4. RNAi design based on,the principle of primer design porcine FoxO1 gene shRNA sequence, synthesis, annealing after the formation of double-stranded oligonucleotides cloned into the lentiviral vector of the sticky end of Lenti H1 vector, sequencing, build FoxO1 gene RNAi lentiviral vector, bjective To construct a lentiviral vector-mediated RNAi of FoxO1 gene and provide the basis for further experiments in muscle fiber types.
引文
[1] Kaestner K H, Kn?chel W, Martinez D E. Unified nomenclature for the winged helix/forkhead transcription factors[J]. Genes & Dev, 2000, 14(2):142-146.
[2] Arden K C, Biggs W H. Regulation of the FoxO family of transcription factors by phosphatidylinositol-3 kinase-activated signaling[J]. Arch Biochem Biophys, 2002, 403 (2): 292-298.
[3] Puig O, Marr M T, Ruhf M L, et al. Control of cell number by drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway[J]. Genes Dev, 2003, 17(16):2006-2020.
[4] Nakae J, Kitamura T, Kitamura Y, et al. The forkhead transcription factor FoxO1 regulates adipocyte differentiation[J]. Dev Cell, 2003, 4(1):119-129.
[5] Brunet A, Sweeney L B, Sturgill J F, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase[J]. Science, 2004, 303(5 666): 2 011-2 015.
[6] Kamei Y, Miura S, Suzuki M, et al. Skeletal muscle FOXO1 (FKHR)-transgenic mice have less skeletal muscle mass, down-regulated type I (slow twitch/red muscle) fiber genes, and impaired glycemic control[J]. J Biol Chem, 2004, 279:41 114-41 123.
[7] Farmer Stephen R. The forkhead transcription factor FoxO1: a possible link between obesity and insulin resistance[J]. Mol Cell, 2003, 11:6-8.
[8] Brikenkamp K U, Coffer P J. FOXO transcription factors as regulators of immune homeostasis: molecules to die for[J]. The Journal of Immunology, 2003, 171(4):1623-1629.
[9] Weigel D,Jackle H.The forkhead domain:anovel DNA binding motif of eukaryotic transcription factors [J] .Cell,1990, 63 (3) :455-456
[10] Junger MA,Rintelen F,Stocker H, et al.The Drosophila Forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling[J].JBiol., 2003, 2(3):20-28
[11] Jacobs FM,vander Heide LP,Wijchers PJ, et al.FoxO6,anovel member of the FoxO class of transcription factors with distinct shuttling dynamics[J].JBiolChem,2003, 278(38) :35959-35967
[12] Accilid A,Arden KC.FoxOs at the crossroads of cellular metabolism, differentiation,and transformation[J] .Cell,2004, 117 (4) :421-426
[13] Kim U Brikenkamp,Paul J Coffer. FOXO transcription factors as regulators of immune homeostasis: molecules to die for? [J]. The Journal of Immunology, 2003, 171(4):1623-1629.
[14] Peter Carlsson, Margit Mahlapuu. Forkhead transcription factors: Key players in development and metabolism [J]. Dev Biol, 2002, 250(l):1-23
[15] Hidalgo A, ffrench-ConstantC. Control of cell number by drosophila FOXO:downstream and feed back regulation of the insulin receptor pathway [J].Mech Dev, 2003, 120(11):1311-1325.
[16] Bois PR, Grosveld GC. FKHR (FOXO1a) is required for myotube fusion of primary mouse myoblasts [J]. EMBO J, 2003, 22 (5): 1147-1157.
[17] Schmidt M,Fernande Z,deMattos S, et al.Cell cycle inhibition by FoxO forkhead transcription factors involves down regulation of cyclin D[J].MolCellBiol,2002, 22(22) :7842-7852
[18] Zhao X, Gan L, Pan H, et al. Multip le elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation and 14-3-3-dependent and independent mechanisms [J]. Biochem J, 2004, 378: 839-849.
[19] Daitoku H, Hatta M,Matsuzaki H, et al.Silent information Regulator 2 potentiates FoxO1-mediated transcription through its deacetylase activity[J].ProcNatlAcadSciUSA,2004, 101(27) : 10042-10047
[20] Jing EX, Gesta S,Kahn CR.SIRT2 regulates adipocyte differentiation through FoxO1acetylation P deacetylation[J].Cell mMetab,2007, 6(2) :105-114
[21] Matsuzaki H,Daitoku H,Hatta M, et al.Acetylation of FoxO1alters its DNA-binding ability and sensitivity tophosphorylation[J].Proc Natl Acad Sci USA,2005, 102(32) :11278-11283
[22] VanderHeide LP,Smidt MP.Regulation of FoxO activity by CBP/P300-mediate dacetylation[J].Trends Biochem Sci,2005, 30 (2) :81-86
[23] Gan L,HanY,Bastianetto S, et al.FoxO dependentand independent mechanism smediate SirT1 effectson IGFBP-1gene expression[J].BiochemBiophysResCommun,2005, 337 (4) :1092-1096
[24] McKinsey TA, Zhang CL, and Olson EN. Control of muscle development by dueling HATs and HDACs [J]. Curr Opin Genet Dev, 2001, 11:497-504.
[25] Bois RJ, Brochard VF, Cleveland JL, et al. FoxO1a–Cyclic GMP-Dependent Kinase I Interactions Orchestrate Myoblast Fusion [J]. Molecular and Cellular Biology, 2005, 25(17):7645-7656.
[26] Nishiyama T, Kii I, and Kudo A. Inactivation of Rho/ROCK signaling is crucial for the nuclear accumulation of FKHR and myoblast fusion [J].J. Biol. Chem, 2004, 279:47311-47319.
[27] Choi SW, Baek MY, and Kang MS. Involvement of cyclic GMP in the fusion of chick embryonic myoblasts in culture [J]. Exp Cell Res, 1992, 199:129-133.
[28] Molkentin JD, and Olson EN. Defining the regulatory networks for muscle development [J]. CurrOpin Genet Dev, 1996, 6:445-453.
[29] Hribal M L, Nakae J, Kitamura T, et al. Regulation of insulin-like growth factor–dependent myoblast differentiation by FoxO forkhead transcription factors[J]. The Journal of Cell Biology, 2003, 162(4):535-541.
[30] Liu CM,Yang Z,Liu CW, et al.Effectof RNA oligo nucleotide targeting FoxO1 on muscle grow thin normaland cancer cachexia mice[J].CancerGeneTher,2007, 14(12) :945-952
[31] Kitamura T,KitamuraYI,FunahashiY, et al.AFoxO Pnotch pathway control smyogenic differentiation and fiber type specification[J].JClinInvest,2007, 117(9) :2477-2485
[32] Lefaucheur L, Milan D, Ecolan P, et al. Myosin heavy chain composition of different skeletal muscles in Large White and Meishan pigs. Journal of animal science. 2004, 82(7): 1931-1941.
[33] Dwyer CM, Fletcher JM, Stickland NC. Muscle cellularity and postnatal growth in the pig[J]. J Anim Sci,1993,71:3339-3343.
[34] Lefaucheur L. Myofiber typing and pig meat production[J]. Slov Vet Res, 2001,38:5-28.
[35] Picard B, Lefaucheur L, Berri C,et al. Muscle fiber ontogenesis in farm animal species[J]. Reprod Nutr Dev, 2002,42:415-431.
[36] Maltin CA, Delday MI, Sinclair KD,et al. Impact of manipulation of myogenesis in utero on the performance of adult skeletal muscle[J]. Reproduction, 2001,122:359-374.
[37] Rehfeldt C, Fiedler I, Dietl G,et al. Myogenesis and postnatal skeletal muscle growth as influenced by selection[J]. Livest Prod Sci, 2000,66:177-188.
[38] Gema Fru hbeck,Pilar Sesma,Mar?′a A. Burrell. PRDM16: the interconvertible adipo-myocyte switch. [J]. Trends in Cell Biology;2009, Vol.19 No.4.
[39] Allen RE,Merkel RA,Young RB.Cellular aspects of muscle growth:myogenic cellProliferation.[J].Anim.Sci;1979,49(l):115-127.
[40] Young VR.Muscle Protein accretion[J].Anim.Sci,1985,61(Supp1.2):39-56.
[41] Brameld MJ, Buttery PJ, Dawson JM,et al. Nutritional and hormonal control of skeletal-muscle cell growth and differentiation[J]. Proc Nutr Soc, 1998,57:207-217.
[42] Nougu`es J. Etude D. Evolution du nombre des fibers musculaires au cours de la croissance post-natale du muscle chez le lapin[J]. CR Soc Biol Montpellier, 1972,166:165-172.
[43] Greenwood PL, Hunt AS, Hermanson JW,et al. Effects of birth weight and postnatalnutrition on neonatal sheep: II. Skeletal muscle growth and development [J]. J Anim Sci, 2000,78:50-61.
[44] McCoard SA, McNabb WC, Peterson SW,et al. Muscle growth, cell number, type and morphometry in single and twin fetal lambs during mid to late gestation [J]. Reprod Fertil Dev, 2000,12:319-327.
[45] Wigmore PM,Stiekland NC.Muscle development in large and small Pig fetues.[J]Anat,1983,137:235- 245
[46] Campion DR,Rjehardson LR,Reagan JO, Kraeling RR.Changes in the Satellite cell PoPulation in fetal pig skeletal muscle.[J].Anim.Sci,1979,48(5):1109-1115.
[47] Campion DR,Riehardson LR,Reagan JO,Kzaeling RR.Changes in thesatellite cell population during postnatal growth of Pig skeletal muscle.[J].Anim.Sci,1981,52(5):1014-1018.
[48] Sabourin LA, Rudnicki MA. The molecular regulation of myogenesis[J]. Clin Genet, 2000, 57: 16-26.
[49] Valdez MR, Richardson JA, Klein WH,et al. Failure of Myf5 to support myogenic differentiation without myogenin, MyoD, and MRF4[J]. Dev Biol, 2000,219:287-298.
[50] Dodou E, Xu SM, Black BL. mef2c is activated directly by myogenic basic helix-loop-helix proteins during skeletal muscle development in vivo[J]. Mech Dev, 2002,120:1021-1032.
[51] Wei Q, Paterson BM. Regulation of MyoD function in the dividing myoblast [J]. FEBS Lett, 2001,490:171-178.
[52] Gao J, Li Z, Paulin D. A novel site, Mt, in the human desmin enhancer is necessary for maximal expression in skelcaal musrae [J]. J Biol Chem, 1998, 273(11):6402-6410.
[53] Kuang W, Xu H, Vachon P H et al. Merosin-deficient congenital muscular dystrophy. Partial genetic correction in two mouse models [J]. J Clin Invest,1998, 102(4):844-851.
[54] Arnold HH, Winter B. Muscle differentiation: more complexity to the network of myogenic regulators [J]. Curr Opin tenet Dew, 1998, 8(5):539-547.
[55] Zhang J M, Chen I, Krausr M et al. Evolutionary conservation of MyoD function and differential utilization of E proteins [J]. Dev Biol,1999, 208 (2):465-473.
[56] Lattanzi L, Salvatnri G, Coletta M, et al. High efficiency myogcnic conversion of hurman fibroblasta by adenoviral vector-mediated MyoD gene transfer. An alternative strategy for ex vivo gene therapy of primary myopathiea [J]. J Clin Invest,1998, 101(10):2119-2127
[57] Barth J L, Morris J, Ivarie R. An Oot like binding factor regulates Myf-5 expression in primary avian cells [J]. Exp Cell Res, 1998, 238 (2):430-438.
[58] Kitzmann M, Vandromme M ,Schaeffer V et al. cdkl and cdk2-medi-ated phosphotylation of MyoD Ser200 in growing C2 myoblasts: role in modulating MyoD half-life and myogenic activity [J]. Mol Cell Biol,1999, 19(4):3167
[59] Ruseo S. Tornatis D, Collo C. et al. Myogenic: conversion of NIH3T3 cells by exogenous MyoD family members: dissaciation of terminal differentiation from myotube forrnation. J Cell Sci,1998,111 (6): 691-701.
[60] Wackerhage H, Woods NM. Exercise-induced signal transduction and gene regulation in skeletal muscle[J]. Journal of Sports Science and Medicine. 2002, 1: 103-114.
[61] Lin Q, Liu I, lauagisawa F, et al. Requirement o1 the MADS-box transcription factor MEF2C for vascular development [J]. Developrnent, 1998, 125(22):4565-4572.
[62] Horycki AC, Li J, Jin F, et al. Pax3 functions in cell survival and in pax7 regulation [J]. Development, 1999, 126(8): 1665-1673.
[63] Muroya S, Nakajima l, Chikuni K.Related expression of MyoD and Myf5 with myosin heavy chain isoform types in bovine adult skeletal museles.Zoo1og Sci, 2002, 19(7):755-761
[64] Eklnark M, Gronevik E, Sehjerling P, Gundersen K.Myogenin induces higher oxidative capacity in pre-xisting mouse muscle fibres after somatic DNA transfer.J Physiol, 2003, 21
[65] Miller J B.Myogenic programs of mouse muscle eell lines:expression of myosin heavy chain isoforms myoD and myogenin.[J]Cell Biol, 1990, 111:1149-1159
[66] Balllman MM, Hill VJ, Adams GR Haddad F, Wetztein CJ, Gower BA, Ahmed A, Hunrer GR. Gender differences in resistance-training-induced myofiber hypertr0Phy among older adults.[J] Gerontol A Biol Sci Med Sci, 2003, 58(2):108-116
[67] Te Pas MF, Soumillion A, Harders FL, Verburg FJ, Van den Boseh TJ, Galesloot P, Meuwissen TH.Influenees of myogenin genotypes on birth weight,growth rate,earcass weight, backfat thickness,and lean weight of PigS.[J].Anim Sci.1999, 77:2352-2356
[68] Wu Z, Jin H, Gu Y.The effect of MyoD family proteins on museular atrophy induced by brachial plexus injury in rats.Zhonghua Yi Xue Za Zhi 2002 APr25:82(8):561-563
[69] Always SE, Degens H, Lowe DA, Krishnamurthy G.Increased myogenic repress or Id mRNA and protein levels inhindlimb muscles of aged rats.Am J physiol Regul Integr ComP physiol 2002, 282(2):R4ll-422
[70] Sakuma K,Watanabe K,Sano M,Uramoto l,Totsuka T.Differential adaptation of GDF8/myostatin,FGF6 and leukemia inhibitory factor in overloaded,regenerating and denervated ra tmuseles.Biochem BioPhy Acta.2000, 1497:77-8.
[71] Carlson CJ, Booth FW, Gordon SE.Skeletal musele myostatin mRNA expression is fiber-type specific and inereases during hindlimb unloading.Am J Physiol, 1999, 277:R601-6.
[72] Wehling M, cai B, Tidball JG.Modulation of myostatin expression during modified muscle use. FASEB [J], 2000, 14:103-110.
[73] GonZalez-Cadavid NF, Taylor WE, Yarasheski K, Sinha-Hikim l, Ma K, Ezzat s, Shen R, Lalani R, Asa S, Mamita M, Nair G, Arver S, Bhasin S.organization of the human myostatin gene and expression in healthy men and HIV-infeeted men with musele wasting.Proe Natl Aead Sci USA,1998, 95: 14938-14943.
[74] Kocamis H,MeFarland DC,Killefer J.Temporal expression of growth factor genes during myogenesis of satellite cells derived from the bicePs femoris and Peetoralis major museles of the chieken.[J]Cell Physiol,2001,186:146-52.
[75] Wu Z,Puigserver P,Andersson U.Meehanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1.Cell,1999,98:115-124
[76] Ek J,Andersen G.Uthammer,SA.Mutation analysis of peroxisome Proliferator-activatedreceptor-gamma coactivator-l(PGC-l)and relationships of ideniified amino acid polymorphisms to TyPeII diabetes mellitus.Diabetologia, 2001,44(12):2220-2226.
[77] Goto M,Terada S,Kato M,Katoh M,YokoZeki T,Tabatal,Shimokawa T.cDNA Cloning and mRNA analysis of PGC-1 in ePitrochlearis musele in swimming-xereised rats.Biochem.BioPhys.Res.Commun,2000,274:350-354.
[78] Baar K.Wende A R,Jones T E,Marison M,Nolte LA,Chen M,Kelly D P,Holloszy JO.AdaPtations of skeletal musele to exereise:rapid increase in the transeriPtional coaCtivator PGC-1.FASEB[J],2002 (16):1879-1886.
[79] Terada S,Goto M,Kato M,Kawanaka K,Shimokawa T,Tabata1.Effeets of low-intensity Prolonged exercise on PGC-1 mRNA exPression in rat ePitrochlearis musele.Biochem.BioPhys.Res.Commun.,2002,(296):350-354.
[80] Tanner CJ, Barakat HA, Dohm GL, et al. Muscle fiber type is associated with obesity and weight loss. Am J Physiol Endocrinol Metab. 2002, 282: 1191-1196.
[81] Czubryt MP, McAnally J, Fishman GI, et al. Regulation of peroxisome proliferator- activated receptorγcoactivator 1α(PGC-1α) and mitochondrial function by MEF2 and HDAC5. Proc. Natl. Acad. Sci. 2003, 100: 1711-1716.
[82] Handschin C, Rhee J, Lin J, et al. An autoregulatory loop controls peroxisome proliferator-activated receptorγcoactivator 1α?expression in muscle. Proc. Natl. Acad. Sci. 2003, 100: 7111-7116.
[83] Hai W, Naya FJ, McKinsey TA, et al. MEF2:responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type. The EMBO Journal. 2000, 19: 1963-1973.
[84] Chang KC. Key signalling factors and pathways in the molecular determination of skeletal muscle phenotype. Animal. 2007, 1: 681-698.
[85] Potthoff MJ, Olson EN. MEF2 a central regulator of diverse developmental programs. Development. 2007, 134: 4131-4140.
[86] Mu X, Brown LD, Liu Y, et al. Roles of the calcineurin and CaMK signaling pathways in fast-to-slow fiber type transformation of cultured adult mouse skeletal muscle fibers. Physiol Genomic. 2007, 30(3): 300-312.
[87] Duby RB, Olson EN. Signaling Pathways in Skeletal Muscle Remodeling. Annu.Rev.Biochem. 2006, 75: 19-37.
[88] Pette, D., and R. S. Staron. Myosin isoforms, muscle fiber types, and transitions. Microsc. Res. Tech. 2000.50:500-509.
[89] Solomon, M. B., and R. L. West. Profile of fiber types in muscles from wild pigs native to the United States. Meat Sci. 1985.13:247-254.
[90] Weiler, U., H. J. Appell, M. Kremser, S. Hofacker, and R. Claus. Consequences of selection on muscle composition. A comparative study on gracilis muscle in wild and domestic pigs .Anat. Histol. Embryol. 1995. 24:77-80.
[91] Wu AL, Kim JH, Zhang CB, et al. Forkhead Box Protein O1 Negatively Regulates Skeletal Myocyte Differentiation through Degradation of Mammalian Target of Rapamycin Pathway Components. Endocrinology. 2008, 149: 1407-1414.
[92]杨燕军,庞卫军,白亮等.八眉、长×八和长白猪肌肉组织中FoxO1基因的表达.遗传. 2008, 28(2): 0253-9772.
[93]庞卫军,杨公社.猪FoxO1基因cDNA的克隆及对前体脂肪细胞和成肌细胞分化的调控作用[D].陕西杨凌西北农林科技大学2007.
[94] Allen D L, Unterman T G. Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD transcription factors [J]. Physiol Cell Physiol, 2007, 292(1):C188-199.
[95] McFarlane C, Plummer E, Thomas M, et al. Myostatin induces cachexia by activating the ubiquitin proteolytic system through an NF-kappaB-independent, FoxO1-dependent mechanism [J]. Cell. Physiol., 2006, 209(2):501-514.
[96] Wu H,Gallardo T,Olson EN,Williams RS,Shohet RV.Transcriptional analysis of mouse skeletal myofiber diversity and adaptation to endurance exercise.[J]Muscle Res Cell Motil.2003 ,24(8):587-592.
[97] Sullivan VK,Powers SK,Criswell DS,tumer N,Larochelle JS,Lowenthal D.Myosin heavy chain composition in young and old rat skeletal muscle:effects of endurance exercise.[J]AppI Physiol.1995,78(6):2115-2120.
[98] Bamman MM,HillVJ,Adams GR,Haddad F,wetzstein CJ,Gower BA,Ahmed A,Hunter GR.Gender differences in resistance-trainining-induced myofiber hypertrophy among older adults.[J]Gerontol A Biol Sci Med Sci,2003,58(2):108-116.
[99] Pang W J,Sun S D,Bai L, et al.Molecular cloning and expression offork head transcription factorO1 gene from pig Susscrofa [J].Asian Aust J Anim Sci,2008,21(4) :499-509
[100] Wei-Jun Pang, Tai-Yong Yu, Liang Bai, et al. Tissue expression of porcine FoxO1 and its negative regulation during primary preadipocyte differentiation[J]. Mol Biol Rep, 2009,36:165-176
[101] Delling U, Tureckova J, Lim HW, et al. A calcineurin-NFATc3-dependent pathway regulates skeletal muscle differentiation and slow myosin heavy-chain expression [J]. Mol Cell Boil, 2000, 20 (17):6600-6611.
[102] Black BL, Molkentin JD, Olson EN. Multiple roles for the MyoD basic region in transmission of transcriptional activation signals and interaction with MEF2C [J]. Mol Cell Biol,1998,18:69-77.
[103] Karasseva, N, Tsika, G, Ji, J, et al. Transcription enhancer factor 1 binds multiple muscle MEF2 and A/T-rich elements during fast-to-slow skeletal muscle fiber type transitions [J]. Mol Cell Biol, 2003,23:5143-5164
[104] Chakkalakal JV, Stocksley MA, Harrison MA, et al. Expression of utrophin A mRNA correlates with the oxidative capacity of skeletal muscle fiber types and is regulated by calcineurin/NFAT signaling [J]. Proc. Natl. Acad. Sci. U. S. A., 2003, 100:7791-7796.
[105] Motta MC, Divecha N, Lemieux M, et al. Mammalian SIRT1 represses forkhead transcription factors [J]. Cell, 2004, 116:551-63.
[106] Giannakou ME, Partridge L. The interaction between FOXO and SIRT1: tipping the balance towards survival [J]. Trends Cell Biol, 2004, 14:408-12.
[107] Fulco M, Schiltz RL, Iezzi S, et al. Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state [J]. Mol Cell, 2003, 12:51-62.
[108] Tanny JC, Moazed D. Coupling of histone deacetylation to NAD breakdown by the yeast silencing protein Sir2: Evidence for acetyl transfer from substrate to an NAD breakdown product [J]. Proc Natl Acad Sci U S A, 2001, 98:415-20.
[109] Cavalieri S, Cazzaniga S, Geuna M, et al. Human T lymphocytes transduced by lentiviral vectors in the absence of TCR activation maintain an intact immune competence. Blood, 2003, 102:497-505
[110] Karasseva N,Tsika G,Ji J,et al.Transcription enhancer factor 1 binds multiple muscle MEF2 and A/T-rich elements during fast-to-slow skeletal muscle fiber type transitions [J]. Mol.Cell. Biol., 2003,23:5143-5164
[111] Marta L,Hribal,Jun Nakae,et al.Regulation of insulin-like growth factor–dependent myoblast differentiation by Foxo forkhead transcription factors.J.Cell. Biol., 2003,18:535-541
[112] Mi-Sung Kim,Jens Fielitz,John McAnally,et al.Protein Kinase D1 Stimulates MEF2 Activity in Skeletal Muscle and Enhances Muscle Performance. Molecular and cellular biology., 2008,p. 3600-3609
[2] Arden K C, Biggs W H. Regulation of the FoxO family of transcription factors by phosphatidylinositol-3 kinase-activated signaling[J]. Arch Biochem Biophys, 2002, 403 (2): 292-298.
[3] Puig O, Marr M T, Ruhf M L, et al. Control of cell number by drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway[J]. Genes Dev, 2003, 17(16):2006-2020.
[4] Nakae J, Kitamura T, Kitamura Y, et al. The forkhead transcription factor FoxO1 regulates adipocyte differentiation[J]. Dev Cell, 2003, 4(1):119-129.
[5] Brunet A, Sweeney L B, Sturgill J F, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase[J]. Science, 2004, 303(5 666): 2 011-2 015.
[6] Kamei Y, Miura S, Suzuki M, et al. Skeletal muscle FOXO1 (FKHR)-transgenic mice have less skeletal muscle mass, down-regulated type I (slow twitch/red muscle) fiber genes, and impaired glycemic control[J]. J Biol Chem, 2004, 279:41 114-41 123.
[7] Farmer Stephen R. The forkhead transcription factor FoxO1: a possible link between obesity and insulin resistance[J]. Mol Cell, 2003, 11:6-8.
[8] Brikenkamp K U, Coffer P J. FOXO transcription factors as regulators of immune homeostasis: molecules to die for[J]. The Journal of Immunology, 2003, 171(4):1623-1629.
[9] Weigel D,Jackle H.The forkhead domain:anovel DNA binding motif of eukaryotic transcription factors [J] .Cell,1990, 63 (3) :455-456
[10] Junger MA,Rintelen F,Stocker H, et al.The Drosophila Forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling[J].JBiol., 2003, 2(3):20-28
[11] Jacobs FM,vander Heide LP,Wijchers PJ, et al.FoxO6,anovel member of the FoxO class of transcription factors with distinct shuttling dynamics[J].JBiolChem,2003, 278(38) :35959-35967
[12] Accilid A,Arden KC.FoxOs at the crossroads of cellular metabolism, differentiation,and transformation[J] .Cell,2004, 117 (4) :421-426
[13] Kim U Brikenkamp,Paul J Coffer. FOXO transcription factors as regulators of immune homeostasis: molecules to die for? [J]. The Journal of Immunology, 2003, 171(4):1623-1629.
[14] Peter Carlsson, Margit Mahlapuu. Forkhead transcription factors: Key players in development and metabolism [J]. Dev Biol, 2002, 250(l):1-23
[15] Hidalgo A, ffrench-ConstantC. Control of cell number by drosophila FOXO:downstream and feed back regulation of the insulin receptor pathway [J].Mech Dev, 2003, 120(11):1311-1325.
[16] Bois PR, Grosveld GC. FKHR (FOXO1a) is required for myotube fusion of primary mouse myoblasts [J]. EMBO J, 2003, 22 (5): 1147-1157.
[17] Schmidt M,Fernande Z,deMattos S, et al.Cell cycle inhibition by FoxO forkhead transcription factors involves down regulation of cyclin D[J].MolCellBiol,2002, 22(22) :7842-7852
[18] Zhao X, Gan L, Pan H, et al. Multip le elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation and 14-3-3-dependent and independent mechanisms [J]. Biochem J, 2004, 378: 839-849.
[19] Daitoku H, Hatta M,Matsuzaki H, et al.Silent information Regulator 2 potentiates FoxO1-mediated transcription through its deacetylase activity[J].ProcNatlAcadSciUSA,2004, 101(27) : 10042-10047
[20] Jing EX, Gesta S,Kahn CR.SIRT2 regulates adipocyte differentiation through FoxO1acetylation P deacetylation[J].Cell mMetab,2007, 6(2) :105-114
[21] Matsuzaki H,Daitoku H,Hatta M, et al.Acetylation of FoxO1alters its DNA-binding ability and sensitivity tophosphorylation[J].Proc Natl Acad Sci USA,2005, 102(32) :11278-11283
[22] VanderHeide LP,Smidt MP.Regulation of FoxO activity by CBP/P300-mediate dacetylation[J].Trends Biochem Sci,2005, 30 (2) :81-86
[23] Gan L,HanY,Bastianetto S, et al.FoxO dependentand independent mechanism smediate SirT1 effectson IGFBP-1gene expression[J].BiochemBiophysResCommun,2005, 337 (4) :1092-1096
[24] McKinsey TA, Zhang CL, and Olson EN. Control of muscle development by dueling HATs and HDACs [J]. Curr Opin Genet Dev, 2001, 11:497-504.
[25] Bois RJ, Brochard VF, Cleveland JL, et al. FoxO1a–Cyclic GMP-Dependent Kinase I Interactions Orchestrate Myoblast Fusion [J]. Molecular and Cellular Biology, 2005, 25(17):7645-7656.
[26] Nishiyama T, Kii I, and Kudo A. Inactivation of Rho/ROCK signaling is crucial for the nuclear accumulation of FKHR and myoblast fusion [J].J. Biol. Chem, 2004, 279:47311-47319.
[27] Choi SW, Baek MY, and Kang MS. Involvement of cyclic GMP in the fusion of chick embryonic myoblasts in culture [J]. Exp Cell Res, 1992, 199:129-133.
[28] Molkentin JD, and Olson EN. Defining the regulatory networks for muscle development [J]. CurrOpin Genet Dev, 1996, 6:445-453.
[29] Hribal M L, Nakae J, Kitamura T, et al. Regulation of insulin-like growth factor–dependent myoblast differentiation by FoxO forkhead transcription factors[J]. The Journal of Cell Biology, 2003, 162(4):535-541.
[30] Liu CM,Yang Z,Liu CW, et al.Effectof RNA oligo nucleotide targeting FoxO1 on muscle grow thin normaland cancer cachexia mice[J].CancerGeneTher,2007, 14(12) :945-952
[31] Kitamura T,KitamuraYI,FunahashiY, et al.AFoxO Pnotch pathway control smyogenic differentiation and fiber type specification[J].JClinInvest,2007, 117(9) :2477-2485
[32] Lefaucheur L, Milan D, Ecolan P, et al. Myosin heavy chain composition of different skeletal muscles in Large White and Meishan pigs. Journal of animal science. 2004, 82(7): 1931-1941.
[33] Dwyer CM, Fletcher JM, Stickland NC. Muscle cellularity and postnatal growth in the pig[J]. J Anim Sci,1993,71:3339-3343.
[34] Lefaucheur L. Myofiber typing and pig meat production[J]. Slov Vet Res, 2001,38:5-28.
[35] Picard B, Lefaucheur L, Berri C,et al. Muscle fiber ontogenesis in farm animal species[J]. Reprod Nutr Dev, 2002,42:415-431.
[36] Maltin CA, Delday MI, Sinclair KD,et al. Impact of manipulation of myogenesis in utero on the performance of adult skeletal muscle[J]. Reproduction, 2001,122:359-374.
[37] Rehfeldt C, Fiedler I, Dietl G,et al. Myogenesis and postnatal skeletal muscle growth as influenced by selection[J]. Livest Prod Sci, 2000,66:177-188.
[38] Gema Fru hbeck,Pilar Sesma,Mar?′a A. Burrell. PRDM16: the interconvertible adipo-myocyte switch. [J]. Trends in Cell Biology;2009, Vol.19 No.4.
[39] Allen RE,Merkel RA,Young RB.Cellular aspects of muscle growth:myogenic cellProliferation.[J].Anim.Sci;1979,49(l):115-127.
[40] Young VR.Muscle Protein accretion[J].Anim.Sci,1985,61(Supp1.2):39-56.
[41] Brameld MJ, Buttery PJ, Dawson JM,et al. Nutritional and hormonal control of skeletal-muscle cell growth and differentiation[J]. Proc Nutr Soc, 1998,57:207-217.
[42] Nougu`es J. Etude D. Evolution du nombre des fibers musculaires au cours de la croissance post-natale du muscle chez le lapin[J]. CR Soc Biol Montpellier, 1972,166:165-172.
[43] Greenwood PL, Hunt AS, Hermanson JW,et al. Effects of birth weight and postnatalnutrition on neonatal sheep: II. Skeletal muscle growth and development [J]. J Anim Sci, 2000,78:50-61.
[44] McCoard SA, McNabb WC, Peterson SW,et al. Muscle growth, cell number, type and morphometry in single and twin fetal lambs during mid to late gestation [J]. Reprod Fertil Dev, 2000,12:319-327.
[45] Wigmore PM,Stiekland NC.Muscle development in large and small Pig fetues.[J]Anat,1983,137:235- 245
[46] Campion DR,Rjehardson LR,Reagan JO, Kraeling RR.Changes in the Satellite cell PoPulation in fetal pig skeletal muscle.[J].Anim.Sci,1979,48(5):1109-1115.
[47] Campion DR,Riehardson LR,Reagan JO,Kzaeling RR.Changes in thesatellite cell population during postnatal growth of Pig skeletal muscle.[J].Anim.Sci,1981,52(5):1014-1018.
[48] Sabourin LA, Rudnicki MA. The molecular regulation of myogenesis[J]. Clin Genet, 2000, 57: 16-26.
[49] Valdez MR, Richardson JA, Klein WH,et al. Failure of Myf5 to support myogenic differentiation without myogenin, MyoD, and MRF4[J]. Dev Biol, 2000,219:287-298.
[50] Dodou E, Xu SM, Black BL. mef2c is activated directly by myogenic basic helix-loop-helix proteins during skeletal muscle development in vivo[J]. Mech Dev, 2002,120:1021-1032.
[51] Wei Q, Paterson BM. Regulation of MyoD function in the dividing myoblast [J]. FEBS Lett, 2001,490:171-178.
[52] Gao J, Li Z, Paulin D. A novel site, Mt, in the human desmin enhancer is necessary for maximal expression in skelcaal musrae [J]. J Biol Chem, 1998, 273(11):6402-6410.
[53] Kuang W, Xu H, Vachon P H et al. Merosin-deficient congenital muscular dystrophy. Partial genetic correction in two mouse models [J]. J Clin Invest,1998, 102(4):844-851.
[54] Arnold HH, Winter B. Muscle differentiation: more complexity to the network of myogenic regulators [J]. Curr Opin tenet Dew, 1998, 8(5):539-547.
[55] Zhang J M, Chen I, Krausr M et al. Evolutionary conservation of MyoD function and differential utilization of E proteins [J]. Dev Biol,1999, 208 (2):465-473.
[56] Lattanzi L, Salvatnri G, Coletta M, et al. High efficiency myogcnic conversion of hurman fibroblasta by adenoviral vector-mediated MyoD gene transfer. An alternative strategy for ex vivo gene therapy of primary myopathiea [J]. J Clin Invest,1998, 101(10):2119-2127
[57] Barth J L, Morris J, Ivarie R. An Oot like binding factor regulates Myf-5 expression in primary avian cells [J]. Exp Cell Res, 1998, 238 (2):430-438.
[58] Kitzmann M, Vandromme M ,Schaeffer V et al. cdkl and cdk2-medi-ated phosphotylation of MyoD Ser200 in growing C2 myoblasts: role in modulating MyoD half-life and myogenic activity [J]. Mol Cell Biol,1999, 19(4):3167
[59] Ruseo S. Tornatis D, Collo C. et al. Myogenic: conversion of NIH3T3 cells by exogenous MyoD family members: dissaciation of terminal differentiation from myotube forrnation. J Cell Sci,1998,111 (6): 691-701.
[60] Wackerhage H, Woods NM. Exercise-induced signal transduction and gene regulation in skeletal muscle[J]. Journal of Sports Science and Medicine. 2002, 1: 103-114.
[61] Lin Q, Liu I, lauagisawa F, et al. Requirement o1 the MADS-box transcription factor MEF2C for vascular development [J]. Developrnent, 1998, 125(22):4565-4572.
[62] Horycki AC, Li J, Jin F, et al. Pax3 functions in cell survival and in pax7 regulation [J]. Development, 1999, 126(8): 1665-1673.
[63] Muroya S, Nakajima l, Chikuni K.Related expression of MyoD and Myf5 with myosin heavy chain isoform types in bovine adult skeletal museles.Zoo1og Sci, 2002, 19(7):755-761
[64] Eklnark M, Gronevik E, Sehjerling P, Gundersen K.Myogenin induces higher oxidative capacity in pre-xisting mouse muscle fibres after somatic DNA transfer.J Physiol, 2003, 21
[65] Miller J B.Myogenic programs of mouse muscle eell lines:expression of myosin heavy chain isoforms myoD and myogenin.[J]Cell Biol, 1990, 111:1149-1159
[66] Balllman MM, Hill VJ, Adams GR Haddad F, Wetztein CJ, Gower BA, Ahmed A, Hunrer GR. Gender differences in resistance-training-induced myofiber hypertr0Phy among older adults.[J] Gerontol A Biol Sci Med Sci, 2003, 58(2):108-116
[67] Te Pas MF, Soumillion A, Harders FL, Verburg FJ, Van den Boseh TJ, Galesloot P, Meuwissen TH.Influenees of myogenin genotypes on birth weight,growth rate,earcass weight, backfat thickness,and lean weight of PigS.[J].Anim Sci.1999, 77:2352-2356
[68] Wu Z, Jin H, Gu Y.The effect of MyoD family proteins on museular atrophy induced by brachial plexus injury in rats.Zhonghua Yi Xue Za Zhi 2002 APr25:82(8):561-563
[69] Always SE, Degens H, Lowe DA, Krishnamurthy G.Increased myogenic repress or Id mRNA and protein levels inhindlimb muscles of aged rats.Am J physiol Regul Integr ComP physiol 2002, 282(2):R4ll-422
[70] Sakuma K,Watanabe K,Sano M,Uramoto l,Totsuka T.Differential adaptation of GDF8/myostatin,FGF6 and leukemia inhibitory factor in overloaded,regenerating and denervated ra tmuseles.Biochem BioPhy Acta.2000, 1497:77-8.
[71] Carlson CJ, Booth FW, Gordon SE.Skeletal musele myostatin mRNA expression is fiber-type specific and inereases during hindlimb unloading.Am J Physiol, 1999, 277:R601-6.
[72] Wehling M, cai B, Tidball JG.Modulation of myostatin expression during modified muscle use. FASEB [J], 2000, 14:103-110.
[73] GonZalez-Cadavid NF, Taylor WE, Yarasheski K, Sinha-Hikim l, Ma K, Ezzat s, Shen R, Lalani R, Asa S, Mamita M, Nair G, Arver S, Bhasin S.organization of the human myostatin gene and expression in healthy men and HIV-infeeted men with musele wasting.Proe Natl Aead Sci USA,1998, 95: 14938-14943.
[74] Kocamis H,MeFarland DC,Killefer J.Temporal expression of growth factor genes during myogenesis of satellite cells derived from the bicePs femoris and Peetoralis major museles of the chieken.[J]Cell Physiol,2001,186:146-52.
[75] Wu Z,Puigserver P,Andersson U.Meehanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1.Cell,1999,98:115-124
[76] Ek J,Andersen G.Uthammer,SA.Mutation analysis of peroxisome Proliferator-activatedreceptor-gamma coactivator-l(PGC-l)and relationships of ideniified amino acid polymorphisms to TyPeII diabetes mellitus.Diabetologia, 2001,44(12):2220-2226.
[77] Goto M,Terada S,Kato M,Katoh M,YokoZeki T,Tabatal,Shimokawa T.cDNA Cloning and mRNA analysis of PGC-1 in ePitrochlearis musele in swimming-xereised rats.Biochem.BioPhys.Res.Commun,2000,274:350-354.
[78] Baar K.Wende A R,Jones T E,Marison M,Nolte LA,Chen M,Kelly D P,Holloszy JO.AdaPtations of skeletal musele to exereise:rapid increase in the transeriPtional coaCtivator PGC-1.FASEB[J],2002 (16):1879-1886.
[79] Terada S,Goto M,Kato M,Kawanaka K,Shimokawa T,Tabata1.Effeets of low-intensity Prolonged exercise on PGC-1 mRNA exPression in rat ePitrochlearis musele.Biochem.BioPhys.Res.Commun.,2002,(296):350-354.
[80] Tanner CJ, Barakat HA, Dohm GL, et al. Muscle fiber type is associated with obesity and weight loss. Am J Physiol Endocrinol Metab. 2002, 282: 1191-1196.
[81] Czubryt MP, McAnally J, Fishman GI, et al. Regulation of peroxisome proliferator- activated receptorγcoactivator 1α(PGC-1α) and mitochondrial function by MEF2 and HDAC5. Proc. Natl. Acad. Sci. 2003, 100: 1711-1716.
[82] Handschin C, Rhee J, Lin J, et al. An autoregulatory loop controls peroxisome proliferator-activated receptorγcoactivator 1α?expression in muscle. Proc. Natl. Acad. Sci. 2003, 100: 7111-7116.
[83] Hai W, Naya FJ, McKinsey TA, et al. MEF2:responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type. The EMBO Journal. 2000, 19: 1963-1973.
[84] Chang KC. Key signalling factors and pathways in the molecular determination of skeletal muscle phenotype. Animal. 2007, 1: 681-698.
[85] Potthoff MJ, Olson EN. MEF2 a central regulator of diverse developmental programs. Development. 2007, 134: 4131-4140.
[86] Mu X, Brown LD, Liu Y, et al. Roles of the calcineurin and CaMK signaling pathways in fast-to-slow fiber type transformation of cultured adult mouse skeletal muscle fibers. Physiol Genomic. 2007, 30(3): 300-312.
[87] Duby RB, Olson EN. Signaling Pathways in Skeletal Muscle Remodeling. Annu.Rev.Biochem. 2006, 75: 19-37.
[88] Pette, D., and R. S. Staron. Myosin isoforms, muscle fiber types, and transitions. Microsc. Res. Tech. 2000.50:500-509.
[89] Solomon, M. B., and R. L. West. Profile of fiber types in muscles from wild pigs native to the United States. Meat Sci. 1985.13:247-254.
[90] Weiler, U., H. J. Appell, M. Kremser, S. Hofacker, and R. Claus. Consequences of selection on muscle composition. A comparative study on gracilis muscle in wild and domestic pigs .Anat. Histol. Embryol. 1995. 24:77-80.
[91] Wu AL, Kim JH, Zhang CB, et al. Forkhead Box Protein O1 Negatively Regulates Skeletal Myocyte Differentiation through Degradation of Mammalian Target of Rapamycin Pathway Components. Endocrinology. 2008, 149: 1407-1414.
[92]杨燕军,庞卫军,白亮等.八眉、长×八和长白猪肌肉组织中FoxO1基因的表达.遗传. 2008, 28(2): 0253-9772.
[93]庞卫军,杨公社.猪FoxO1基因cDNA的克隆及对前体脂肪细胞和成肌细胞分化的调控作用[D].陕西杨凌西北农林科技大学2007.
[94] Allen D L, Unterman T G. Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD transcription factors [J]. Physiol Cell Physiol, 2007, 292(1):C188-199.
[95] McFarlane C, Plummer E, Thomas M, et al. Myostatin induces cachexia by activating the ubiquitin proteolytic system through an NF-kappaB-independent, FoxO1-dependent mechanism [J]. Cell. Physiol., 2006, 209(2):501-514.
[96] Wu H,Gallardo T,Olson EN,Williams RS,Shohet RV.Transcriptional analysis of mouse skeletal myofiber diversity and adaptation to endurance exercise.[J]Muscle Res Cell Motil.2003 ,24(8):587-592.
[97] Sullivan VK,Powers SK,Criswell DS,tumer N,Larochelle JS,Lowenthal D.Myosin heavy chain composition in young and old rat skeletal muscle:effects of endurance exercise.[J]AppI Physiol.1995,78(6):2115-2120.
[98] Bamman MM,HillVJ,Adams GR,Haddad F,wetzstein CJ,Gower BA,Ahmed A,Hunter GR.Gender differences in resistance-trainining-induced myofiber hypertrophy among older adults.[J]Gerontol A Biol Sci Med Sci,2003,58(2):108-116.
[99] Pang W J,Sun S D,Bai L, et al.Molecular cloning and expression offork head transcription factorO1 gene from pig Susscrofa [J].Asian Aust J Anim Sci,2008,21(4) :499-509
[100] Wei-Jun Pang, Tai-Yong Yu, Liang Bai, et al. Tissue expression of porcine FoxO1 and its negative regulation during primary preadipocyte differentiation[J]. Mol Biol Rep, 2009,36:165-176
[101] Delling U, Tureckova J, Lim HW, et al. A calcineurin-NFATc3-dependent pathway regulates skeletal muscle differentiation and slow myosin heavy-chain expression [J]. Mol Cell Boil, 2000, 20 (17):6600-6611.
[102] Black BL, Molkentin JD, Olson EN. Multiple roles for the MyoD basic region in transmission of transcriptional activation signals and interaction with MEF2C [J]. Mol Cell Biol,1998,18:69-77.
[103] Karasseva, N, Tsika, G, Ji, J, et al. Transcription enhancer factor 1 binds multiple muscle MEF2 and A/T-rich elements during fast-to-slow skeletal muscle fiber type transitions [J]. Mol Cell Biol, 2003,23:5143-5164
[104] Chakkalakal JV, Stocksley MA, Harrison MA, et al. Expression of utrophin A mRNA correlates with the oxidative capacity of skeletal muscle fiber types and is regulated by calcineurin/NFAT signaling [J]. Proc. Natl. Acad. Sci. U. S. A., 2003, 100:7791-7796.
[105] Motta MC, Divecha N, Lemieux M, et al. Mammalian SIRT1 represses forkhead transcription factors [J]. Cell, 2004, 116:551-63.
[106] Giannakou ME, Partridge L. The interaction between FOXO and SIRT1: tipping the balance towards survival [J]. Trends Cell Biol, 2004, 14:408-12.
[107] Fulco M, Schiltz RL, Iezzi S, et al. Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state [J]. Mol Cell, 2003, 12:51-62.
[108] Tanny JC, Moazed D. Coupling of histone deacetylation to NAD breakdown by the yeast silencing protein Sir2: Evidence for acetyl transfer from substrate to an NAD breakdown product [J]. Proc Natl Acad Sci U S A, 2001, 98:415-20.
[109] Cavalieri S, Cazzaniga S, Geuna M, et al. Human T lymphocytes transduced by lentiviral vectors in the absence of TCR activation maintain an intact immune competence. Blood, 2003, 102:497-505
[110] Karasseva N,Tsika G,Ji J,et al.Transcription enhancer factor 1 binds multiple muscle MEF2 and A/T-rich elements during fast-to-slow skeletal muscle fiber type transitions [J]. Mol.Cell. Biol., 2003,23:5143-5164
[111] Marta L,Hribal,Jun Nakae,et al.Regulation of insulin-like growth factor–dependent myoblast differentiation by Foxo forkhead transcription factors.J.Cell. Biol., 2003,18:535-541
[112] Mi-Sung Kim,Jens Fielitz,John McAnally,et al.Protein Kinase D1 Stimulates MEF2 Activity in Skeletal Muscle and Enhances Muscle Performance. Molecular and cellular biology., 2008,p. 3600-3609