异丙肾上腺素通过NF-kappaB通路延缓失神经骨骼肌萎缩
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摘要
目的研究异丙肾上腺素、对核转录因子kappaB (nuclear factor of kappaB, NF-kappaB)p65和E3连接酶MAFbx活性的影响,探讨各种药物防治肌萎缩的作用及其机制
方法选择健康的雄性SD大鼠54只,体重195±5g,随机分为A,B,C,D,E,F,G,H,I 9组,每组6只。A组为对照组(假手术组),B、C、D,E组为去神经组,F、G,H,I为异丙肾上腺素组。大鼠分批用戊巴比妥钠(40mg/kg, ip)麻醉后,用右下肢后部中段切断坐骨神经的方法制作失神经骨骼肌动物模型,正常组仅做假手术(不切断坐骨神经),去神经组及异丙肾上腺素组切断坐骨神经1cm以上,分别于去神经第2d、7d、14d、28d处死大鼠(用脊椎脱臼法),用显微外科技术认真游离失神经腓肠肌,切取的肌肉样本快速置于-80℃冰箱冻存,备用。用RT-PCR法检测MAFbx与NF-KB的mRNA:以GAPDH作为内参照,做半定量检测。取样本组织50mg匀浆后用上海生工抽提试剂进行总RNA抽提,然后用MBI的RT-PCR试剂盒,按样本RNA2μg,20μl体系进行反转录。MAFbx其上游引物：5'cta cga tgt tgc agc caa ga 3',下游引物：5'Ggc agt cga gaa gtc cag tc:3',共167bp；P65的上游引物：5'gac cag gaa gtc agc gag tc3’下游引物：5'tcc aga ggg aca get ctt gt3’共176bp.作为内参照的GAPDH的引物由山西医科大学实验中心提供,其上游引物：5'tga acg gga agc tca ctg g 3',下游引物：5'tcc acc acc ctg ttg ctg ta 3',共307bp.聚合酶链反应按50μl体系,反应条件为：96℃,2′, 1cycle。96℃,30″; Tm(Myf-5 53℃)/(GAPDH 50℃),30″; 72℃,2′,36 cycle。用免疫印迹法(Westernblot法)测定MAFbx与NF-KB的蛋白质：用β-actin作为内参照,做半定量检测。取样本组织100mg匀浆后用普利莱蛋白提取试剂盒进行总蛋白抽提,煮沸、离心后,加样于垂直电泳槽行SDS-PAGE,电泳约3h,转膜1小时30分钟,封闭室温4小时,孵育一抗(Ab1)4℃过夜,漂洗后孵育二抗(Ab2)4℃约4小时,TBS漂洗后,置于暗室加ECL发光试剂盒反应,一分钟左右立即放在暗箱曝光,60秒左右取出浸入显影剂内,观察至最佳显影后,捞出在清水中洗净,然后置于定影剂中15分钟,取出晾干后用数码相机获取图片。最后用NIH的ImageJ软件获取数据,用SPSS软件进行统计分析。
结果去神经骨骼肌萎缩时,腓肠肌MAFbx、NF-KB的mRNA和蛋白质在去神经支配后第2d、7d、14d、28d不同时段表达均为上调。NF-KB药物各组与失神经组同时段比较均下调(除2d组外)P<0.05,而MAFbx表达无统计学意义,P>0.05.结论大鼠失神经骨骼肌萎缩早期,MAFbx、NF-KB的表达在腓肠肌为上调,异丙肾上腺素是通过NF-KB途径来防治失神经早期的骨骼肌萎缩的。
Objective To study the influence of Isoprenaline on the expression pattern of nuclear factor of kappaB (NF-kappaB) and muscle atrophy F-box MAFbx and explore the preventive and therapeutic effect and mechanisms of Isoprenaline on denervated skeletal muscle atrophy.
Method A total of 54 healthy male and 8w age Sprague-Duwley rats were selected. They have 195±5g weight and were devided randomly into nine group, A control group (innervations)、experimental B group (denervated 2d)、experimental C group (denervated 7d)、experimental D group (denervated 14d), experimental E group (denervated 28d) Isoprenaline F group (denervated 2d)、Isoprenaline G group (denervated 7d)、Isoprenaline H group (denervated 14d), Isoprenaline J group (denervated 28d) six rats in every group. After the rats were anesthetized by pentobarbital sodium (40mg/kg) intraperitoneal injection in batch, The midpiece_sciatic nerve of their right lower limb posterior part were cut off for making animal model of denervated skeletal muscle. Sham operation was made only for the rats in normal group (sciatic nerve were not cut off) and sciatic nerve were cut off more than one centimeter for the rats in denervated group. The rats were executed by vertebrae dislocation method in batch. The rats in control group and experimental a group were executed in 48 hour after operation, experimental B and F group for seven day, experimental C and G group for twenty-eight day and so on. whereafter muscle specimen were quickly placed in -80℃refrigerator for reserve. MAFbx and NF-kappaB mRNA level detected by RT-PCR: GAPDH,as a inner reference, are used to make semiquantitative detection for Myf-5mRNA.Take 50mg sample tissue to homogenate, and then extract total RNA by extract reagent from shanhai sangon,next to have it inversely transcripted by RT-PCR reagent box from MBI according as 2μl sample RNA and 20μl system. MAFbx primer derives from primer5.0 software design. the upper stream primer is 5'cta cga tgt tgc agc caa ga 3', the downstream primer is 5'Ggc agt cga gaa gtc cag tc3', 167bp.P65:5'gac cag gaa gtc agc gag tc 3'. the downstream primer is:5'tcc aga ggg aca get ctt gt 3',176bp.As a inner reference,GAPDH primer come from Shanxi medical university molecule experiment centre and its piece length have 308bp. polymerase chain reaction goes on by 50μl system and its reaction condition as follow:96℃,2',1cycle。96℃-30″; Tm(Myf-5 53℃)/(GAPDH 50℃)-30″; 72℃,2′,36 cycle. MyoD protein level detected by Westernblot:β-actin,as a inner reference, are used to make semiquantitative detection for MAFbx and NF-kappaB protein. Take 100mg sample tissue to homogenate, and then extract total protein by protein extract reagent box from Applygen Technologies Inc. after boiled for 5min and centrifugated in sample buffer for 10 min,RNA samples were spotted into pore of vertical electrophoresis bath and were separated in 12% SDS-PAGE for about three hour and transferred onto nitrocellulose membrane (Bio-Rad) for 1 hour and thirty minutes.Nonspecific reactivity was blocked by incubation 4h at 20℃in buffer(10mM Tris-HCl, pH7.5,150mM NaCl, 2%Tween-20,4% bovine sreum albumin).After floating in TBST buffer, The membrane was then incubated with primary antibody overnight at 4℃. After floating in TBST buffer, The secondary antibody was used to incubated with the membrane for 4h at 4℃. After floating in TBST buffer and TBS buffer, The membrane was then placed in dark room and reactive protein was detected by ECL chemiluminescence system(santa cruz). the membrane was immediately placed into camera obscure for exposition about 1 min,and was taken out to immerse into developer until developing was optimization. then the membrane was immediately got out of the developer, placed into fixerfor about fifteen minutes, taken out for open-air drying, photographed by figure camera for store.Finally,ImageJ software from NIH was used to get image data about mean grey value.then SPSS software-was used to statistics ordered data by one-way anova analysis. Sigmaplot software was used to statistics plotting.
Result Expression of MAFbx、NF-κB mRNA and protein all are up-regulation at 2d、7d、14d、28d after denervation. The effect shows that only the expression of NF-κB mRNA and protein level in specimens of Isoprenaline group are down-regulated at 2d、7d、14d、28d after denervation compared with that in denervation Group (P<0.05).
Conclusion:Expression of MAFbx、NF-κB were up-regulation at 2、7、14、28 days after denervation In the early stage of skeletal muscles.only NF-κB expression of gastrocnemius denervation model of rats can be down-regulated by Isoprenaline, which shows that Isoprenaline is a effective way of delaying denervated skeletal muscle atrophy through participate in NF-κB path.
方法选择健康的雄性SD大鼠54只,体重195±5g,随机分为A,B,C,D,E,F,G,H,I 9组,每组6只。A组为对照组(假手术组),B、C、D,E组为去神经组,F、G,H,I为异丙肾上腺素组。大鼠分批用戊巴比妥钠(40mg/kg, ip)麻醉后,用右下肢后部中段切断坐骨神经的方法制作失神经骨骼肌动物模型,正常组仅做假手术(不切断坐骨神经),去神经组及异丙肾上腺素组切断坐骨神经1cm以上,分别于去神经第2d、7d、14d、28d处死大鼠(用脊椎脱臼法),用显微外科技术认真游离失神经腓肠肌,切取的肌肉样本快速置于-80℃冰箱冻存,备用。用RT-PCR法检测MAFbx与NF-KB的mRNA:以GAPDH作为内参照,做半定量检测。取样本组织50mg匀浆后用上海生工抽提试剂进行总RNA抽提,然后用MBI的RT-PCR试剂盒,按样本RNA2μg,20μl体系进行反转录。MAFbx其上游引物：5'cta cga tgt tgc agc caa ga 3',下游引物：5'Ggc agt cga gaa gtc cag tc:3',共167bp；P65的上游引物：5'gac cag gaa gtc agc gag tc3’下游引物：5'tcc aga ggg aca get ctt gt3’共176bp.作为内参照的GAPDH的引物由山西医科大学实验中心提供,其上游引物：5'tga acg gga agc tca ctg g 3',下游引物：5'tcc acc acc ctg ttg ctg ta 3',共307bp.聚合酶链反应按50μl体系,反应条件为：96℃,2′, 1cycle。96℃,30″; Tm(Myf-5 53℃)/(GAPDH 50℃),30″; 72℃,2′,36 cycle。用免疫印迹法(Westernblot法)测定MAFbx与NF-KB的蛋白质：用β-actin作为内参照,做半定量检测。取样本组织100mg匀浆后用普利莱蛋白提取试剂盒进行总蛋白抽提,煮沸、离心后,加样于垂直电泳槽行SDS-PAGE,电泳约3h,转膜1小时30分钟,封闭室温4小时,孵育一抗(Ab1)4℃过夜,漂洗后孵育二抗(Ab2)4℃约4小时,TBS漂洗后,置于暗室加ECL发光试剂盒反应,一分钟左右立即放在暗箱曝光,60秒左右取出浸入显影剂内,观察至最佳显影后,捞出在清水中洗净,然后置于定影剂中15分钟,取出晾干后用数码相机获取图片。最后用NIH的ImageJ软件获取数据,用SPSS软件进行统计分析。
结果去神经骨骼肌萎缩时,腓肠肌MAFbx、NF-KB的mRNA和蛋白质在去神经支配后第2d、7d、14d、28d不同时段表达均为上调。NF-KB药物各组与失神经组同时段比较均下调(除2d组外)P<0.05,而MAFbx表达无统计学意义,P>0.05.结论大鼠失神经骨骼肌萎缩早期,MAFbx、NF-KB的表达在腓肠肌为上调,异丙肾上腺素是通过NF-KB途径来防治失神经早期的骨骼肌萎缩的。
Objective To study the influence of Isoprenaline on the expression pattern of nuclear factor of kappaB (NF-kappaB) and muscle atrophy F-box MAFbx and explore the preventive and therapeutic effect and mechanisms of Isoprenaline on denervated skeletal muscle atrophy.
Method A total of 54 healthy male and 8w age Sprague-Duwley rats were selected. They have 195±5g weight and were devided randomly into nine group, A control group (innervations)、experimental B group (denervated 2d)、experimental C group (denervated 7d)、experimental D group (denervated 14d), experimental E group (denervated 28d) Isoprenaline F group (denervated 2d)、Isoprenaline G group (denervated 7d)、Isoprenaline H group (denervated 14d), Isoprenaline J group (denervated 28d) six rats in every group. After the rats were anesthetized by pentobarbital sodium (40mg/kg) intraperitoneal injection in batch, The midpiece_sciatic nerve of their right lower limb posterior part were cut off for making animal model of denervated skeletal muscle. Sham operation was made only for the rats in normal group (sciatic nerve were not cut off) and sciatic nerve were cut off more than one centimeter for the rats in denervated group. The rats were executed by vertebrae dislocation method in batch. The rats in control group and experimental a group were executed in 48 hour after operation, experimental B and F group for seven day, experimental C and G group for twenty-eight day and so on. whereafter muscle specimen were quickly placed in -80℃refrigerator for reserve. MAFbx and NF-kappaB mRNA level detected by RT-PCR: GAPDH,as a inner reference, are used to make semiquantitative detection for Myf-5mRNA.Take 50mg sample tissue to homogenate, and then extract total RNA by extract reagent from shanhai sangon,next to have it inversely transcripted by RT-PCR reagent box from MBI according as 2μl sample RNA and 20μl system. MAFbx primer derives from primer5.0 software design. the upper stream primer is 5'cta cga tgt tgc agc caa ga 3', the downstream primer is 5'Ggc agt cga gaa gtc cag tc3', 167bp.P65:5'gac cag gaa gtc agc gag tc 3'. the downstream primer is:5'tcc aga ggg aca get ctt gt 3',176bp.As a inner reference,GAPDH primer come from Shanxi medical university molecule experiment centre and its piece length have 308bp. polymerase chain reaction goes on by 50μl system and its reaction condition as follow:96℃,2',1cycle。96℃-30″; Tm(Myf-5 53℃)/(GAPDH 50℃)-30″; 72℃,2′,36 cycle. MyoD protein level detected by Westernblot:β-actin,as a inner reference, are used to make semiquantitative detection for MAFbx and NF-kappaB protein. Take 100mg sample tissue to homogenate, and then extract total protein by protein extract reagent box from Applygen Technologies Inc. after boiled for 5min and centrifugated in sample buffer for 10 min,RNA samples were spotted into pore of vertical electrophoresis bath and were separated in 12% SDS-PAGE for about three hour and transferred onto nitrocellulose membrane (Bio-Rad) for 1 hour and thirty minutes.Nonspecific reactivity was blocked by incubation 4h at 20℃in buffer(10mM Tris-HCl, pH7.5,150mM NaCl, 2%Tween-20,4% bovine sreum albumin).After floating in TBST buffer, The membrane was then incubated with primary antibody overnight at 4℃. After floating in TBST buffer, The secondary antibody was used to incubated with the membrane for 4h at 4℃. After floating in TBST buffer and TBS buffer, The membrane was then placed in dark room and reactive protein was detected by ECL chemiluminescence system(santa cruz). the membrane was immediately placed into camera obscure for exposition about 1 min,and was taken out to immerse into developer until developing was optimization. then the membrane was immediately got out of the developer, placed into fixerfor about fifteen minutes, taken out for open-air drying, photographed by figure camera for store.Finally,ImageJ software from NIH was used to get image data about mean grey value.then SPSS software-was used to statistics ordered data by one-way anova analysis. Sigmaplot software was used to statistics plotting.
Result Expression of MAFbx、NF-κB mRNA and protein all are up-regulation at 2d、7d、14d、28d after denervation. The effect shows that only the expression of NF-κB mRNA and protein level in specimens of Isoprenaline group are down-regulated at 2d、7d、14d、28d after denervation compared with that in denervation Group (P<0.05).
Conclusion:Expression of MAFbx、NF-κB were up-regulation at 2、7、14、28 days after denervation In the early stage of skeletal muscles.only NF-κB expression of gastrocnemius denervation model of rats can be down-regulated by Isoprenaline, which shows that Isoprenaline is a effective way of delaying denervated skeletal muscle atrophy through participate in NF-κB path.
引文
[1]A.J. Murton, D. Constantin, P.L. Greenhaff The involvement of the ubiquitin protremodelling and atrophy Biochimica et Biophysica Acta 1782 2008,730-743
[2]Katoch SS, Garg A, Sharma S. Indian J Exp Biol. Histological evidences of reparative and regenerative effects of beta-adrenoceptor agonists, clenbuterol and isoproterenol, in denervated rat skeletal muscle. 2006 Jun;44(6):448-58.
[3]Garg A, Sharma S. Isoproterenol ameliorates workstress-induced rat skeletal muscle degeneration.2006 Apr;43(2):82-7.
[4]David J. Glass Skeletal muscle hypertrophy and atrophy signaling pathways. The International Journal of Biochemistry & Cell Biology 37 2005,1974-1984
[5]Hershko, A., Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem,1998.67,425-427
[6]Bodine, S.C., Latres, E., Baumhueter, S., et al. Identification of ubiquitin ligases required for skeletal muscle atrophy.2001,Science 294,1704-1708.
[7]Gomes, M.D.Lecker, S.H Jagoe, R.T, et al. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy, Proc. Natl.Acad.Sci. U. S. A.98 (2001) 14440-14445.
[8]Li HH, Willis MS, Lockyer P,et al.Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins. J Clin Invest 2007; 117:3211-23.
[9]Okada A, Ono Y, Nagatomi R, et al.Decreased muscle atrophy F-box (MAFbx) expression in regenerating muscle after muscle-damaging exercise 2008 Oct;38(4):1246-53.
[10]Zhao W, Pan J, Wang X, Wu Y, Bauman WA, Cardozo CP. Expression of the muscle atrophy factor muscle atrophy F-box is suppressed by testosterone.2008, Jul 3149(11):5449-60.
[11]Williamson, D. L., Kimball, S. R., Jefferson, L. S.Acute treatment with TNF-{alpha} attenuates insulin-stimulatedprotein synthesis in cultures of C2C12 myotubes through aMEK1-sensitive mechanism.Am. J. Physiol. Endocrinol.Metab.,2005,E95-E104.
[12]Li, Y.-P., Chen, Y, John, J.et al. TNF-{alpha} acts via p38 MAPK to stimulate expression of the ubiquitin ligase atroginl/MAFbx in skeletal muscle.FASEB J.,2005.19,362-370
[13]Mikura M, Yamaoka I, Doi M, Kawano Y, et al. Glucose infusion suppresses surgery-induced muscle protein breakdown by inhibiting ubiquitin-proteasome pathway in rats.2009 Jan;110(1):81-84.
[1]Caamano J, Hunter CA. NF-kappaB family of transcription fac2tors:cent ral regulators of innate and adaptive immune functions[J]. Clin Microbiol Rev,2002 Jul;15(3):414-29.
[2]Hershko, A., Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem,1998.67,425-427
[3]Elledge, S. J., and Harper, J. W. (1998) Biochim. Biophys. Acta 1377,61-70
[4]Ciechanover, A. The ubiquitin-proteasome pathway:on protein death and cell life.(1998) EMBO J.17, 7151-7160
[5]Skowyra, D., Craig, K. L., Tyers, M. et al. F-box proteins are receptors that recruit phosphorylated
substrates to the SCF ubiquitin-ligase comple. (1997)Cell 2,209-219
[6]Skowyra, D., Craig, K. L., Tyers, M. et al. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase comple. (1997)Cell 2,209-219
[7]M.D. Gomes, S.H. Lecker, R.T. Jagoe, A. et al. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy, Proc. Natl. Acad.Sci. U. S. A.98 (2001) 14440-14445.
[8]Guo S, Fan Y, Zhang H, Gu D, Li H.Pathology, Chinese Academy of Medical Sciences, Peking Union Medical College.2008 Dec;13(12):1401-9
[9]Mikura M, Yamaoka I, Doi M,. et al.New Product and Business Development, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Tokushima, Japan.2009 Jan;110(1):81-8.
[10]Okada A, Ono Y, Nagatomi R,. et al.Department of Orthopaedic Surgery, Tohoku University School of Medicine, Seiryo-machi 1-1, Aobaku, Sendai 980-8574, Japan.2008 Oct;38(4):1246-53.
[11]Zhao W, Pan J, Wang X, et al.Center of Excellence for the Medical Consequences of SCI, James J. Peters Veter, ans Affairs Medical Center, Bronx, New York 10468, USA.2008 Nov;149(11):54-60.
[12].Cenciarelli C, Wilhelm KG Jr, Guo A, Weissman AM. T cell antigen receptor ubiquitination is a consequence of receptor-mediated tyrosine kinase activation.J Biol Chem.1996 Apr12;271(15):8709-13.
[13]Wilson, J. T., Koepp, D. M., Zhu, C., A family of mammalian F-box proteins.(1999)Curr. Biol.9, 1180-1182
[14]Batonnet S, Leibovitch MP, Tintignac L, et al.Critical role for lysine 133 in the nuclear ubiquitin-mediated degradation of MyoD. Biol Chem.2004 Feb 13;279(7):5413-20.
[15]Argiles, J. M.,& Lopez-Soriano, F. J. The role of cytokinesin cancer cachexia. Med. Res. (1999). Rev., 19,223-248.
[16]vonHaehling, S.,Genth-Zotz, S.,Anker, S.D. et al:A therapeutic approach beyond cytokine antagonism.Int. J. Cardiol.,85,173-183.
[17]Ladner, K. J., Caligiuri, M. A.,& Guttridge, D. C. Tumornecrosis factor-regulated biphasic activation of NF-kappa B is required for cytokine-induced loss of skeletal muscle gene products. J. Biol. Chem. (2003),278,2294-2303.
[18]Rodriguez JE, Schisler JC, Patterson C, et al. Seek and destroy:the ubiquitin-proteasome system in cardiac disease.Curr Hypertens Rep.2009 Dec;11(6):396-405.
[19]Stitt, T. N., Drujan, D., Clarke, B. A, et al. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases byinhibiting FOXO transcription factors. Mol. Cell., (2004) 14, 395-403.
[20]Lionel A. Tintignac, Julie Lagirand. LeibovitchNovember 5,2004, DOI 10.1074/jbc.M411346200
[21]Sandri M, Sandri C, Gilbert A, Skurk C. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 2004; 117:399-412.
[22]Jonathan C. Schisler,MAFbx/Atrogin-1 feeds forwardonFOXOtranscription factors (like a record) Cell Cycle, Feb(2008); 7:4,440-443.
[21]Cai, D., Frantz, J. D., Tawa, N. E., Jr, et al. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell, (2004),119,285-298.
[22]Li, Y. P., Chen, Y., John, J., Moylan, J.,, et al. TNF-{alpha} acts via p38 MAPK to stimulate expression of the ubiquitin ligase atroginl/MAFbx in skeletal muscle.FASEB J. (2005) 19,362-370.
[23]A.J. Murton, D. Constantin, P.L. Greenhaff The involvement of the ubiquitin protremodelling and atrophy Biochimica et Biophysica Acta 1782 (2008) 730-743
1 Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. The International Journal of Biochemistry & Cell Biology 37 (2005) 1974-1984
2 Birkenkamp,K.U.,&Coffer, P. J. Regulation of cell survival and proliferation by the FOXO(Forkhead box, classO) subfamilyof Forkhead transcription factors. Biochem. Soc. Trans. (2003),31(Pt 1),292-297.
3 Biggs, W. H., Ⅲ, Cavenee, W. K.,& Arden, K. C. Identification and characterization of members of the FKHR (FOXO) subclass of winged-helix transcription factors in the mouse.Mamm. Genome, (200 1),12(6),416-425
4 Jacobs, F. M., van der Heide, L. P., Wijchers, P. J. FoxO6, a novel member of the FoxO class of transcription factors with distinct shuttlingdynamics. J. Biol. Chem. (2003).278(38),35959-35967.
5 Van Der Heide, L. P., Hoekman, M. F.,& Smidt, M. P. Theins and outs of FoxO shuttling:mechanisms of FoxO translocation and transcriptional regulation. Biochem. J. (2004),380(Pt 2),297-309.
6 Nader GA. Molecular determinants of skeletal muscle mass:getting the "AKT" together.The International Journal of Biochemistry & Cell Biology 37 (2005) 1985-1996
7 Marco Sandri,Claudia Sandri,Alex Gilbert. Foxo Transcription Factors Induce the Atrophy-Related Ubiquitin Ligase Atrogin-land Cause Skeletal Muscle Atrophy Cell, (2004),Vol.117,399-412
8 Stitt, T. N., Drujan, D., Clarke, B. A., et al. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol. Cell, (2004),14 (3),395-403
9 Lecker, S. H., Jagoe, R. T., Gilbert, A. et al. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression.2004 Jan;18(1):39-51
10 Jonathan C. Schisler, Montem S. et al. MAFbx/Atrogin-1 feeds forward on FOXO transcription factors (like a record) Cell Cycle,(2008) 7:4,440-443
11 Ni YG, Berenji K, Wang N, O, et al., Rothermel BA, Hill JA. Foxo transcription factors blunt cardiac hypertrophy by inhibiting calcineurin signaling. Circulation 2006; 114:1159-68.
12 Li HH, Willis MS, Lockyer P, et al. Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins. J Clin Invest 2007; 117:3211-23
13 Zhao J, Brault JJ, Schild A, et al.Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.2007 Dec;6(6):472-83
14 Zhao J, Brault JJ, Schild A, Goldberg AL.Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.2008 Apr 1;4(3):378-80.
15 Mammucari C, Schiaffino S, Sandri M.Venetian Institute of Molecular Medicine, Padova, Italy.2008 May 16;4(4):524-6.
16 Waddell DS, Baehr LM, van den Brandt J,.Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California 95616, USA.2008 Oct;295(4):E785-97.
17 Crossland H, Constantin-Teodosiu D, Gardiner SM,.Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK. mbxhc@nottingham.ac.uk2008 Nov 15;586(Pt 22):5589-600.
18 Mammucari C, Schiaffino S, Sandri M.Venetian Institute of Molecular Medicine, Padova, Italy.2008 May 16;4(4):524-6.
1 Pallafacchina, G., Calabria, E., Serrano, A. L. A protein kinase B-dependent andrapamycin-sensitive pathway controls skeletal muscle growthbut not fiber type specification.2002 Jul 9;99(14).
2 Hannan, K. M., Thomas, G.,& Pearson, R. B.. Activation of S6K1 (p70 ribosomal protein S6 kinase 1) requires an initial calcium-dependent priming event involving formation of a high-molecular-mass signalling complex. Biochem. J(2003),370,469-477.
3 Kubica, N., Bolster, D. R., Farrell, P. A. Resistance exercise increases muscle protein synthesis and translation of eukaryotic initiation factor 2B{epsilon}mRNA in a mammalian target of rapamycin-dependent mannerJ. Biol. Chem.,(2005) 280,7570-7580.
4 Rochat,A.,Femandez,A.,Vandromme,M.,Moles,J.P.,T.G.C.,&Lamb,N. J. Insulin andwntl pathways cooperateto induce reserve cell activation in differentiation and myotubehypertrophy. Mol. Biol. Cell. (2004),15,4544-455
5 Hershko, A., Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem,1998.67,425-427
6 Elledge, S. J., and Harper, J. W. (1998) Biochim. Biophys. Acta 1377,61-70
7 Ciechanover, A. The ubiquitin-proteasome pathway:on protein death and cell life. (1998) EMBO J.17, 7151-7160
8 Skowyra, D., Craig, K. L., Tyers, M. et al. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase comple. (1997)Cell 2,209-219
9 Skowyra, D., Craig, K. L., Tyers, M. et al. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase comple. (1997)Cell 2,209-219
10 M.D. Gomes, S.H. Lecker, R.T. Jagoe, A. Navon, A.L. Goldberg, Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy, Proc. Natl. Acad.Sci. U. S. A.98 (2001) 14440-14445.
11 Marco Sandri,Claudia Sandri,Alex Gilbert,Foxo Transcription Factors Inducethe Atrophy-Related Ubiquitin Ligase Atrogin-1 and Cause Skeletal Muscle Atrophy Cell, Vol.117,399-412
12 Williamson, D. L., Kimball, S. R.,& Jefferson, L. S.Acute treatment with TNF-{alpha} attenuates insulin-stimulated protein synthesis in cultures of C2C12 myotubes through a MEK1-sensitive mechanism.Am. J. Physiol. Endocrinol.Metab. (2005),E95-E104
13 Mitchell, P. O.,& Pavlath, G. K. Skeletal muscle atrophy leads to loss and dysfunction of muscle precursor cells. Am. J.Physiol. Cell. Physiol.(2004).287, C1753-C1762.
14 Cai, D., Frantz, J. D., Tawa, N. E. et al. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell, (2004).119,285-298.
15 Li, Y.-P., Chen, Y., John, J., Moylan, J. et al. TNF-{alpha} acts via p38 MAPK to stimulate expression of the ubiquitin ligase atroginl/MAFbx in skeletal muscle.FASEB J.(2005) 19,362-370.
16 Amirouche A, Durieux AC, Banzet S, et al.Pole de Recherche et d'Enseignement Superieur Universite de Lyon, Universite Jean Monnet, Laboratoire de Physiologie de l'Exercice, Equipe d'accueil, Saint Etienne, France.2009 Jan;150(1):286-94.
17 Mammucari C, Schiaffino S, Sandri M.Venetian Institute of Molecular Medicine, Padova, Italy.2008 May 16;4(4):524-6.
18 Miyazaki M, Noguchi M, Takemasa T.Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA.2008 May;40(5):848-55.
19 Lamon S, Wallace MA, Leger B,Regulation of STARS and its downstream targets suggest a novel pathway involved in human skeletal muscle hypertrophy and atrophy.2009 Apr 15;587(Pt 8):1795-803.
20 David J. Two tales concerning skeletal muscle Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA. Citationfor thisarticle:J. Clin. Invest. (2007).117:2388-2391
21 MJ Tisdale*,1 Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2a may signal skeletal muscle atrophy in weight-losing cancer patients British Journal of Cancer (2008) 98,443-449
22 Jonathan C. Schisler, Monte S. Willis and Cam Patterson Carolina Cardiovascular Biology Center and Division of Cardiology; University of North Carolina; Chapel Hill, North Carolina USA MAFbx/Atrogin-1 feeds forward on FOXO transcription factors (like a record) [Cell Cycle 7:4, 440-443;
23 LionelA. Tintignac, Julie Lagirand,, et al,Degradation of MyoD Mediated by the SCF (MAFbx) Ubiquitin Ligase S Received for publication, October 5,2004, and in revised form, October 28,2004 Published, JBC Papers in Press, November 5,2004, DOI 10.1074/jbc.M411346200
24 Hong Li & Shweta Malhotra & Ashok,Nuclear factor-kappa B signaling in skeletal muscle atrophy KumarReceived:Mol Med.2008 Oct;86(10):1113-26
1 Arnold HH winter B. Muscle differentiation:more complexity to the network of myogenic regulators Curr Opin Genet Dev.1998 Oct;8(5):539-44.
2Gruss P, Walther C. Pax in development cell 1992;69:719-722
3 Wozniak AC, Anderson JE. Nitric oxide dependence of satellite stem cell activation and quiescence on normal skeletal muscle fibers. Dev Dyn 2007;236(1):240-250
4 Bischoff,Ishiko T, Umemura Y, et al. Five jumps per day in-crease bone mass and breaking force in mouse [J]. Bone Min-er,2003,10(2):1321-1331.
5Grounds MD. Muscle regeneration:molecular aspects and therapeutic implications (J). Curr Opin Neurol,1999;12:535-6.
6 park kw.waki H.Id2 is a small molecule-inducible modulator of PPAR{gamma} expression and adipocyte differentiation.2008 Sep;22(9):2038-48.
7 Ji M,Sun HC.Id2 intrinsicallyregulates lymphoid and erythroid development via interaction with different target proteins.Blood.2008 Aug 15;112(4):1068-77.
8Hua H,Sarvetnick N.ID2 promotes the expansion and survival of growth-arrested pancreatic beta cells.Endocrine.2007 Dec;32(3):329-37.
9 LinksTsunedomi R, Iizuka N, Decreased ID2 promotes metastatic potentials of hepatocellular carcinoma by altering secretion of vascular endothelial growth factor.Clin Cancer Res.2008 Feb 15;14(4):1025-31.
10 LinksCotta CV, Leventaki V, Atsaves V,.The helix-loop-helix protein Id2 is expressed differentially and induced by myc in T-cell lymphomas.Cancer.2008 Feb 1;112(3):552-61.
11 Links Zhu X, Lin Y, Chai R, Interleukin-1 beta-induced Id2 gene expression is mediated by Egr-1 in vascular smooth muscle cells.Cardiovasc Res.2007 Oct 1;76(1).
12 Links Moskowitz IP, A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development.Cell.2007 Jun 29;129(7):1365-76.
13 Links Lim JY, Kim WH, Kim J, Induction of Id2 expression by cardiac transcription factors GATA4 and Nkx2.5.J Cell Biochem.2008 Jan 1;103(1):182-94.
14 Links Boos MD, Yokota Y, Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity.J Exp Med.2007 May 14;204(5):1119-30.15 Links Mikami S, Hirose Y, Yoshida K, Predominant expression of OLIG2 over ID2 in oligodendroglial tumors.Virchows Arch.2007 May;450(5):575-84.
16 Links Memezawa A, Takada I,Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes. Oncogene.2007 Aug 2;26(35):5038-45.
17 LinksCannarile MA, Transcriptional regulator Id2 mediates CD8+T cell immunity.Nat Immunol.2006 Dec;7(12):1317-25.
18LinksEraso E, Sahand IH, Villar-Vidal M Usefulness of Candida ID2 agar for the presumptive identification of Candida dubliniensis. Med Mycol.2006 Nov;44(7):611-5
19 LinksPark HR, Jung WW Upregulation of the oncogenic helix-loop-helix protein Id2 in Ewing sarcoma.Tumori.2006 May-Jun;92(3):236-40.
20 LinksLasorella A, Stegmuller J, Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth.Nature.2006 Jul 27;442(7101):471-4.
21 Links Rodri guez JL, Id2 leaves the chromatin of the E2F4-p130-controlled c-myc promoter during hepatocyte priming for liver regeneration..2006 Sep 15;398(3):431-7.
22 Links Jankiewicz M, Mammalian target of rapamycin regulates the growth of mammary epithelial cells through the inhibitor of deoxyribonucleic acid binding Id1 and their functional differentiation through Id2.Mol Endocrinol.2006 Oct;20(10):2369-81.
23 Links Degens H, Swisher AK Apoptosis and Id2 expression in diaphragm and soleus muscle from the emphysematous hamster.Am J Physiol Regul Integr Comp Physiol.2007 Jul;293(l):R135-44.
24 Always SE,Martyn JK,OuyangJ,etal. Id2 expression during apoptosis and satellite cell activation in unloaded and loaded quail skeletal muscles. Am J Physiol Regul Integr Physiol,2003 Feb;284(2):R540-9
[2]Katoch SS, Garg A, Sharma S. Indian J Exp Biol. Histological evidences of reparative and regenerative effects of beta-adrenoceptor agonists, clenbuterol and isoproterenol, in denervated rat skeletal muscle. 2006 Jun;44(6):448-58.
[3]Garg A, Sharma S. Isoproterenol ameliorates workstress-induced rat skeletal muscle degeneration.2006 Apr;43(2):82-7.
[4]David J. Glass Skeletal muscle hypertrophy and atrophy signaling pathways. The International Journal of Biochemistry & Cell Biology 37 2005,1974-1984
[5]Hershko, A., Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem,1998.67,425-427
[6]Bodine, S.C., Latres, E., Baumhueter, S., et al. Identification of ubiquitin ligases required for skeletal muscle atrophy.2001,Science 294,1704-1708.
[7]Gomes, M.D.Lecker, S.H Jagoe, R.T, et al. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy, Proc. Natl.Acad.Sci. U. S. A.98 (2001) 14440-14445.
[8]Li HH, Willis MS, Lockyer P,et al.Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins. J Clin Invest 2007; 117:3211-23.
[9]Okada A, Ono Y, Nagatomi R, et al.Decreased muscle atrophy F-box (MAFbx) expression in regenerating muscle after muscle-damaging exercise 2008 Oct;38(4):1246-53.
[10]Zhao W, Pan J, Wang X, Wu Y, Bauman WA, Cardozo CP. Expression of the muscle atrophy factor muscle atrophy F-box is suppressed by testosterone.2008, Jul 3149(11):5449-60.
[11]Williamson, D. L., Kimball, S. R., Jefferson, L. S.Acute treatment with TNF-{alpha} attenuates insulin-stimulatedprotein synthesis in cultures of C2C12 myotubes through aMEK1-sensitive mechanism.Am. J. Physiol. Endocrinol.Metab.,2005,E95-E104.
[12]Li, Y.-P., Chen, Y, John, J.et al. TNF-{alpha} acts via p38 MAPK to stimulate expression of the ubiquitin ligase atroginl/MAFbx in skeletal muscle.FASEB J.,2005.19,362-370
[13]Mikura M, Yamaoka I, Doi M, Kawano Y, et al. Glucose infusion suppresses surgery-induced muscle protein breakdown by inhibiting ubiquitin-proteasome pathway in rats.2009 Jan;110(1):81-84.
[1]Caamano J, Hunter CA. NF-kappaB family of transcription fac2tors:cent ral regulators of innate and adaptive immune functions[J]. Clin Microbiol Rev,2002 Jul;15(3):414-29.
[2]Hershko, A., Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem,1998.67,425-427
[3]Elledge, S. J., and Harper, J. W. (1998) Biochim. Biophys. Acta 1377,61-70
[4]Ciechanover, A. The ubiquitin-proteasome pathway:on protein death and cell life.(1998) EMBO J.17, 7151-7160
[5]Skowyra, D., Craig, K. L., Tyers, M. et al. F-box proteins are receptors that recruit phosphorylated
substrates to the SCF ubiquitin-ligase comple. (1997)Cell 2,209-219
[6]Skowyra, D., Craig, K. L., Tyers, M. et al. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase comple. (1997)Cell 2,209-219
[7]M.D. Gomes, S.H. Lecker, R.T. Jagoe, A. et al. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy, Proc. Natl. Acad.Sci. U. S. A.98 (2001) 14440-14445.
[8]Guo S, Fan Y, Zhang H, Gu D, Li H.Pathology, Chinese Academy of Medical Sciences, Peking Union Medical College.2008 Dec;13(12):1401-9
[9]Mikura M, Yamaoka I, Doi M,. et al.New Product and Business Development, Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Tokushima, Japan.2009 Jan;110(1):81-8.
[10]Okada A, Ono Y, Nagatomi R,. et al.Department of Orthopaedic Surgery, Tohoku University School of Medicine, Seiryo-machi 1-1, Aobaku, Sendai 980-8574, Japan.2008 Oct;38(4):1246-53.
[11]Zhao W, Pan J, Wang X, et al.Center of Excellence for the Medical Consequences of SCI, James J. Peters Veter, ans Affairs Medical Center, Bronx, New York 10468, USA.2008 Nov;149(11):54-60.
[12].Cenciarelli C, Wilhelm KG Jr, Guo A, Weissman AM. T cell antigen receptor ubiquitination is a consequence of receptor-mediated tyrosine kinase activation.J Biol Chem.1996 Apr12;271(15):8709-13.
[13]Wilson, J. T., Koepp, D. M., Zhu, C., A family of mammalian F-box proteins.(1999)Curr. Biol.9, 1180-1182
[14]Batonnet S, Leibovitch MP, Tintignac L, et al.Critical role for lysine 133 in the nuclear ubiquitin-mediated degradation of MyoD. Biol Chem.2004 Feb 13;279(7):5413-20.
[15]Argiles, J. M.,& Lopez-Soriano, F. J. The role of cytokinesin cancer cachexia. Med. Res. (1999). Rev., 19,223-248.
[16]vonHaehling, S.,Genth-Zotz, S.,Anker, S.D. et al:A therapeutic approach beyond cytokine antagonism.Int. J. Cardiol.,85,173-183.
[17]Ladner, K. J., Caligiuri, M. A.,& Guttridge, D. C. Tumornecrosis factor-regulated biphasic activation of NF-kappa B is required for cytokine-induced loss of skeletal muscle gene products. J. Biol. Chem. (2003),278,2294-2303.
[18]Rodriguez JE, Schisler JC, Patterson C, et al. Seek and destroy:the ubiquitin-proteasome system in cardiac disease.Curr Hypertens Rep.2009 Dec;11(6):396-405.
[19]Stitt, T. N., Drujan, D., Clarke, B. A, et al. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases byinhibiting FOXO transcription factors. Mol. Cell., (2004) 14, 395-403.
[20]Lionel A. Tintignac, Julie Lagirand. LeibovitchNovember 5,2004, DOI 10.1074/jbc.M411346200
[21]Sandri M, Sandri C, Gilbert A, Skurk C. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 2004; 117:399-412.
[22]Jonathan C. Schisler,MAFbx/Atrogin-1 feeds forwardonFOXOtranscription factors (like a record) Cell Cycle, Feb(2008); 7:4,440-443.
[21]Cai, D., Frantz, J. D., Tawa, N. E., Jr, et al. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell, (2004),119,285-298.
[22]Li, Y. P., Chen, Y., John, J., Moylan, J.,, et al. TNF-{alpha} acts via p38 MAPK to stimulate expression of the ubiquitin ligase atroginl/MAFbx in skeletal muscle.FASEB J. (2005) 19,362-370.
[23]A.J. Murton, D. Constantin, P.L. Greenhaff The involvement of the ubiquitin protremodelling and atrophy Biochimica et Biophysica Acta 1782 (2008) 730-743
1 Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. The International Journal of Biochemistry & Cell Biology 37 (2005) 1974-1984
2 Birkenkamp,K.U.,&Coffer, P. J. Regulation of cell survival and proliferation by the FOXO(Forkhead box, classO) subfamilyof Forkhead transcription factors. Biochem. Soc. Trans. (2003),31(Pt 1),292-297.
3 Biggs, W. H., Ⅲ, Cavenee, W. K.,& Arden, K. C. Identification and characterization of members of the FKHR (FOXO) subclass of winged-helix transcription factors in the mouse.Mamm. Genome, (200 1),12(6),416-425
4 Jacobs, F. M., van der Heide, L. P., Wijchers, P. J. FoxO6, a novel member of the FoxO class of transcription factors with distinct shuttlingdynamics. J. Biol. Chem. (2003).278(38),35959-35967.
5 Van Der Heide, L. P., Hoekman, M. F.,& Smidt, M. P. Theins and outs of FoxO shuttling:mechanisms of FoxO translocation and transcriptional regulation. Biochem. J. (2004),380(Pt 2),297-309.
6 Nader GA. Molecular determinants of skeletal muscle mass:getting the "AKT" together.The International Journal of Biochemistry & Cell Biology 37 (2005) 1985-1996
7 Marco Sandri,Claudia Sandri,Alex Gilbert. Foxo Transcription Factors Induce the Atrophy-Related Ubiquitin Ligase Atrogin-land Cause Skeletal Muscle Atrophy Cell, (2004),Vol.117,399-412
8 Stitt, T. N., Drujan, D., Clarke, B. A., et al. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol. Cell, (2004),14 (3),395-403
9 Lecker, S. H., Jagoe, R. T., Gilbert, A. et al. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression.2004 Jan;18(1):39-51
10 Jonathan C. Schisler, Montem S. et al. MAFbx/Atrogin-1 feeds forward on FOXO transcription factors (like a record) Cell Cycle,(2008) 7:4,440-443
11 Ni YG, Berenji K, Wang N, O, et al., Rothermel BA, Hill JA. Foxo transcription factors blunt cardiac hypertrophy by inhibiting calcineurin signaling. Circulation 2006; 114:1159-68.
12 Li HH, Willis MS, Lockyer P, et al. Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins. J Clin Invest 2007; 117:3211-23
13 Zhao J, Brault JJ, Schild A, et al.Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.2007 Dec;6(6):472-83
14 Zhao J, Brault JJ, Schild A, Goldberg AL.Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.2008 Apr 1;4(3):378-80.
15 Mammucari C, Schiaffino S, Sandri M.Venetian Institute of Molecular Medicine, Padova, Italy.2008 May 16;4(4):524-6.
16 Waddell DS, Baehr LM, van den Brandt J,.Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California 95616, USA.2008 Oct;295(4):E785-97.
17 Crossland H, Constantin-Teodosiu D, Gardiner SM,.Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK. mbxhc@nottingham.ac.uk2008 Nov 15;586(Pt 22):5589-600.
18 Mammucari C, Schiaffino S, Sandri M.Venetian Institute of Molecular Medicine, Padova, Italy.2008 May 16;4(4):524-6.
1 Pallafacchina, G., Calabria, E., Serrano, A. L. A protein kinase B-dependent andrapamycin-sensitive pathway controls skeletal muscle growthbut not fiber type specification.2002 Jul 9;99(14).
2 Hannan, K. M., Thomas, G.,& Pearson, R. B.. Activation of S6K1 (p70 ribosomal protein S6 kinase 1) requires an initial calcium-dependent priming event involving formation of a high-molecular-mass signalling complex. Biochem. J(2003),370,469-477.
3 Kubica, N., Bolster, D. R., Farrell, P. A. Resistance exercise increases muscle protein synthesis and translation of eukaryotic initiation factor 2B{epsilon}mRNA in a mammalian target of rapamycin-dependent mannerJ. Biol. Chem.,(2005) 280,7570-7580.
4 Rochat,A.,Femandez,A.,Vandromme,M.,Moles,J.P.,T.G.C.,&Lamb,N. J. Insulin andwntl pathways cooperateto induce reserve cell activation in differentiation and myotubehypertrophy. Mol. Biol. Cell. (2004),15,4544-455
5 Hershko, A., Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem,1998.67,425-427
6 Elledge, S. J., and Harper, J. W. (1998) Biochim. Biophys. Acta 1377,61-70
7 Ciechanover, A. The ubiquitin-proteasome pathway:on protein death and cell life. (1998) EMBO J.17, 7151-7160
8 Skowyra, D., Craig, K. L., Tyers, M. et al. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase comple. (1997)Cell 2,209-219
9 Skowyra, D., Craig, K. L., Tyers, M. et al. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase comple. (1997)Cell 2,209-219
10 M.D. Gomes, S.H. Lecker, R.T. Jagoe, A. Navon, A.L. Goldberg, Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy, Proc. Natl. Acad.Sci. U. S. A.98 (2001) 14440-14445.
11 Marco Sandri,Claudia Sandri,Alex Gilbert,Foxo Transcription Factors Inducethe Atrophy-Related Ubiquitin Ligase Atrogin-1 and Cause Skeletal Muscle Atrophy Cell, Vol.117,399-412
12 Williamson, D. L., Kimball, S. R.,& Jefferson, L. S.Acute treatment with TNF-{alpha} attenuates insulin-stimulated protein synthesis in cultures of C2C12 myotubes through a MEK1-sensitive mechanism.Am. J. Physiol. Endocrinol.Metab. (2005),E95-E104
13 Mitchell, P. O.,& Pavlath, G. K. Skeletal muscle atrophy leads to loss and dysfunction of muscle precursor cells. Am. J.Physiol. Cell. Physiol.(2004).287, C1753-C1762.
14 Cai, D., Frantz, J. D., Tawa, N. E. et al. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell, (2004).119,285-298.
15 Li, Y.-P., Chen, Y., John, J., Moylan, J. et al. TNF-{alpha} acts via p38 MAPK to stimulate expression of the ubiquitin ligase atroginl/MAFbx in skeletal muscle.FASEB J.(2005) 19,362-370.
16 Amirouche A, Durieux AC, Banzet S, et al.Pole de Recherche et d'Enseignement Superieur Universite de Lyon, Universite Jean Monnet, Laboratoire de Physiologie de l'Exercice, Equipe d'accueil, Saint Etienne, France.2009 Jan;150(1):286-94.
17 Mammucari C, Schiaffino S, Sandri M.Venetian Institute of Molecular Medicine, Padova, Italy.2008 May 16;4(4):524-6.
18 Miyazaki M, Noguchi M, Takemasa T.Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA.2008 May;40(5):848-55.
19 Lamon S, Wallace MA, Leger B,Regulation of STARS and its downstream targets suggest a novel pathway involved in human skeletal muscle hypertrophy and atrophy.2009 Apr 15;587(Pt 8):1795-803.
20 David J. Two tales concerning skeletal muscle Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA. Citationfor thisarticle:J. Clin. Invest. (2007).117:2388-2391
21 MJ Tisdale*,1 Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2a may signal skeletal muscle atrophy in weight-losing cancer patients British Journal of Cancer (2008) 98,443-449
22 Jonathan C. Schisler, Monte S. Willis and Cam Patterson Carolina Cardiovascular Biology Center and Division of Cardiology; University of North Carolina; Chapel Hill, North Carolina USA MAFbx/Atrogin-1 feeds forward on FOXO transcription factors (like a record) [Cell Cycle 7:4, 440-443;
23 LionelA. Tintignac, Julie Lagirand,, et al,Degradation of MyoD Mediated by the SCF (MAFbx) Ubiquitin Ligase S Received for publication, October 5,2004, and in revised form, October 28,2004 Published, JBC Papers in Press, November 5,2004, DOI 10.1074/jbc.M411346200
24 Hong Li & Shweta Malhotra & Ashok,Nuclear factor-kappa B signaling in skeletal muscle atrophy KumarReceived:Mol Med.2008 Oct;86(10):1113-26
1 Arnold HH winter B. Muscle differentiation:more complexity to the network of myogenic regulators Curr Opin Genet Dev.1998 Oct;8(5):539-44.
2Gruss P, Walther C. Pax in development cell 1992;69:719-722
3 Wozniak AC, Anderson JE. Nitric oxide dependence of satellite stem cell activation and quiescence on normal skeletal muscle fibers. Dev Dyn 2007;236(1):240-250
4 Bischoff,Ishiko T, Umemura Y, et al. Five jumps per day in-crease bone mass and breaking force in mouse [J]. Bone Min-er,2003,10(2):1321-1331.
5Grounds MD. Muscle regeneration:molecular aspects and therapeutic implications (J). Curr Opin Neurol,1999;12:535-6.
6 park kw.waki H.Id2 is a small molecule-inducible modulator of PPAR{gamma} expression and adipocyte differentiation.2008 Sep;22(9):2038-48.
7 Ji M,Sun HC.Id2 intrinsicallyregulates lymphoid and erythroid development via interaction with different target proteins.Blood.2008 Aug 15;112(4):1068-77.
8Hua H,Sarvetnick N.ID2 promotes the expansion and survival of growth-arrested pancreatic beta cells.Endocrine.2007 Dec;32(3):329-37.
9 LinksTsunedomi R, Iizuka N, Decreased ID2 promotes metastatic potentials of hepatocellular carcinoma by altering secretion of vascular endothelial growth factor.Clin Cancer Res.2008 Feb 15;14(4):1025-31.
10 LinksCotta CV, Leventaki V, Atsaves V,.The helix-loop-helix protein Id2 is expressed differentially and induced by myc in T-cell lymphomas.Cancer.2008 Feb 1;112(3):552-61.
11 Links Zhu X, Lin Y, Chai R, Interleukin-1 beta-induced Id2 gene expression is mediated by Egr-1 in vascular smooth muscle cells.Cardiovasc Res.2007 Oct 1;76(1).
12 Links Moskowitz IP, A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development.Cell.2007 Jun 29;129(7):1365-76.
13 Links Lim JY, Kim WH, Kim J, Induction of Id2 expression by cardiac transcription factors GATA4 and Nkx2.5.J Cell Biochem.2008 Jan 1;103(1):182-94.
14 Links Boos MD, Yokota Y, Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity.J Exp Med.2007 May 14;204(5):1119-30.15 Links Mikami S, Hirose Y, Yoshida K, Predominant expression of OLIG2 over ID2 in oligodendroglial tumors.Virchows Arch.2007 May;450(5):575-84.
16 Links Memezawa A, Takada I,Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes. Oncogene.2007 Aug 2;26(35):5038-45.
17 LinksCannarile MA, Transcriptional regulator Id2 mediates CD8+T cell immunity.Nat Immunol.2006 Dec;7(12):1317-25.
18LinksEraso E, Sahand IH, Villar-Vidal M Usefulness of Candida ID2 agar for the presumptive identification of Candida dubliniensis. Med Mycol.2006 Nov;44(7):611-5
19 LinksPark HR, Jung WW Upregulation of the oncogenic helix-loop-helix protein Id2 in Ewing sarcoma.Tumori.2006 May-Jun;92(3):236-40.
20 LinksLasorella A, Stegmuller J, Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth.Nature.2006 Jul 27;442(7101):471-4.
21 Links Rodri guez JL, Id2 leaves the chromatin of the E2F4-p130-controlled c-myc promoter during hepatocyte priming for liver regeneration..2006 Sep 15;398(3):431-7.
22 Links Jankiewicz M, Mammalian target of rapamycin regulates the growth of mammary epithelial cells through the inhibitor of deoxyribonucleic acid binding Id1 and their functional differentiation through Id2.Mol Endocrinol.2006 Oct;20(10):2369-81.
23 Links Degens H, Swisher AK Apoptosis and Id2 expression in diaphragm and soleus muscle from the emphysematous hamster.Am J Physiol Regul Integr Comp Physiol.2007 Jul;293(l):R135-44.
24 Always SE,Martyn JK,OuyangJ,etal. Id2 expression during apoptosis and satellite cell activation in unloaded and loaded quail skeletal muscles. Am J Physiol Regul Integr Physiol,2003 Feb;284(2):R540-9