力学因素对细胞自噬的影响
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摘要
背景:心肌肥大、椎间盘退行性疾病等疾病的发生与其组织细胞所处力学环境密切相关,而自噬在这些疾病的发病过程起到重要作用。目的:综述力学因素对不同组织细胞自噬的影响及其涉及的分子机制,为自噬的研究及相关疾病的预防治疗提供参考作用。方法:检索2000至2016年Web of Science和Pub Med数据库中关于力学因素对细胞自噬影响的文献,英文检索词为"autophagy,mechanical",进行系统的归纳总结和分析,排除内容相关性差或重复文献,最终得到52篇文献。结果与结论:(1)力学因素对心肌细胞、内皮细胞、软骨细胞、骨骼肌细胞等多种细胞的自噬产生影响,细胞自噬是细胞应对刺激的一种自我保护性反应,在受到生理水平的力学刺激时,细胞上调自噬水平,维持细胞的稳态、功能以及存活;(2)力学因素可能通过PI3K-AKT-mTOR、氧自由基、AKT-FoxO等通路引起细胞自噬,具体机制有待进一步研究。
BACKGROUND: Numerous diseases like cardiac hypertrophy and intervertebral disc degeneration are known to be implicated in the changes of mechanical stress acting on surrounding tissues or cells, and autophagy contributes to the pathogenesis of these diseases. OBJECTIVE: To review the effects of mechanical factors on autophagy in different tissues and the underlying molecular mechanisms, thereby providing references for the research of autophagy and the prevention and treatment of related diseases. METHODS: A search of Web of Science and Pub Med databases was performed for the literatures addressing the effects of mechanical factors on autophagy using the English keywords of "autophagy, mechanical" and the articles were summarized systematically. Finally, 52 literatures were enrolled according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION: Mechanical factors make great effects on autophagy of various cells, such as myocardial cells, endothelial cells, chondrocytes and skeletal muscle cells. Autophagy is a self-protective reaction, and the mechanical stress of physiological conditions induces autophagy to maintain cell homeostasis, normal function and survival. The mechanism of autophagy induced by mechanical stress may involve PI3K-AKT-m TOR, oxygen free radical, AKT-FoxO and other pathways, and the definite mechanism needs to be further studied.
BACKGROUND: Numerous diseases like cardiac hypertrophy and intervertebral disc degeneration are known to be implicated in the changes of mechanical stress acting on surrounding tissues or cells, and autophagy contributes to the pathogenesis of these diseases. OBJECTIVE: To review the effects of mechanical factors on autophagy in different tissues and the underlying molecular mechanisms, thereby providing references for the research of autophagy and the prevention and treatment of related diseases. METHODS: A search of Web of Science and Pub Med databases was performed for the literatures addressing the effects of mechanical factors on autophagy using the English keywords of "autophagy, mechanical" and the articles were summarized systematically. Finally, 52 literatures were enrolled according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION: Mechanical factors make great effects on autophagy of various cells, such as myocardial cells, endothelial cells, chondrocytes and skeletal muscle cells. Autophagy is a self-protective reaction, and the mechanical stress of physiological conditions induces autophagy to maintain cell homeostasis, normal function and survival. The mechanism of autophagy induced by mechanical stress may involve PI3K-AKT-m TOR, oxygen free radical, AKT-FoxO and other pathways, and the definite mechanism needs to be further studied.
引文
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[16]Weng LQ,Zhang WB,Ye Y,et al.Aliskiren ameliorates pressure overload-induced heart hypertrophy and fibrosis in mice.Acta Pharmacol Sin.2014;35:1005-1014.
[17]Lin L,Liu XB,Xu JF,et al.High-density lipoprotein inhibits mechanical stress-induced cardiomyocyte autophagy and cardiac hypertrophy through angiotensin II type 1receptor-mediated PI3K/Akt pathway.J Cell Mol Med.2015;19:1929-1938.
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[19]Hariharan N,Ikeda Y,Hong C,et al.Autophagy Plays an Essential Role in Mediating Regression of Hypertrophy during Unloading of the Heart.Plos One.2013;8(1):e51632.
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[21]Baskin KK,Rodriguez MR,Kansara S,et al.MAFbx/Atrogin-1is required for atrophic remodeling of the unloaded heart.J Mol Cell Cardiol.2014;72:168-176.
[22]Kassiotis C,Ballal K,Wellnitz K,et al.Markers of Autophagy Are Downregulated in Failing Human Heart After Mechanical Unloading.Circulation.2009;120:S191-S197.
[23]Hill JA.Autophagy in cardiac plasticity and disease.Pediatr Cardiol.2011;32:282-289.
[24]Hariharan N,Maejima Y,Nakae J,et al.Deacetylation of Fox O by Sirt1 Plays an Essential Role in Mediating Starvation-Induced Autophagy in Cardiac Myocytes.Circ Res.2010;107:1470-1482.
[25]Skurk C,Izumiya Y,Maatz H,et al.The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling.J Biol Chem.2005;280:20814-20823.
[26]Sandri M,Sandri C,Gilbert A,et al.Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1and cause skeletal muscle atrophy.Cell.2004;117:399-412.
[27]Mammucari C,Milan G,Romanello V,et al.Fox O3 controls autophagy in skeletal muscle in vivo.Cell Metab.2007;6:458-471.
[28]Zhang HF,Bosch-Marce M,Shimoda LA,et al.Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia.J Biol Chem.2008;283:10892-10903.
[29]Porrello ER,D'amore A,Curl CL,et al.Angiotensin II type 2receptor antagonizes angiotensin II type 1 receptor-mediated cardiomyocyte autophagy.Hypertension.2009;53:1032-1040.
[30]Yadav A,Vallabu S,Arora S,et al.ANG II promotes autophagy in podocytes.Am J Physiol Cell Physiol.2010;299C488-C496.
[31]Huang J,Sun W,Huang H,et al.mi R-34a modulates angiotensin II-induced myocardial hypertrophy by direct inhibition of ATG9A expression and autophagic activity.PLo S One.2014;9(4):e94382.
[32]Yue H,Li W,Desnoyer R,et al.Role of nuclear unphosphorylated STAT3 in angiotensin II type 1 receptorinduced cardiac hypertrophy.Cardiovasc Res.2010;85:90-99.
[33]Ramakrishnan P,Hecht BA,Pedersen DR,et al.Oxidant conditioning protects cartilage from mechanically induced damage.J Orthop Res.2010;28:914-920.
[34]Thomas CM,Fuller CJ,Whittles CE,et al.Chondrocyte death by apoptosis is associated with cartilage matrix degradation.Osteoarthr Cartilage.2007;15:27-34.
[35]Carames B,Taniguchi N,Seino D,et al.Mechanical Injury Suppresses Autophagy Regulators and Pharmacologic Activation of Autophagy Results in Chondroprotection.Arthritis Rheumus.2012;64:1182-192.
[36]Xu HG,Yu YF,Zheng Q,et al.Autophagy protects end plate chondrocytes from intermittent cyclic mechanical tension induced calcification.Bone.2014;66:232-239.
[37]Pan S.Molecular mechanisms responsible for the atheroprotective effects of laminar shear stress.Antioxid Redox Sign.2009;11:1669-1682.
[38]Guo FX,Li XH,Peng J,et al.Autophagy Regulates Vascular Endothelial Cell e NOS and ET-1 Expression Induced by Laminar Shear Stress in an Ex Vivo Perfused System.Ann Biomed Eng.2014;42:1978-1988.
[39]Ding Z,Liu S,Deng X,et al.Hemodynamic shear stress modulates endothelial cell autophagy:Role of LOX-1.Int J Cardiol.2015;184:86-95.
[40]Bharath LP,Mueller R,Li Y,et al.Impairment of autophagy in endothelial cells prevents shear-stress-induced increases in nitric oxide bioavailability.Can J Physiol Pharmacol.2014;92:605-612.
[41]Gumucio JP,Davis ME,Bradley JR,et al.Rotator cuff tear reduces muscle fiber specific force production and induces macrophage accumulation and autophagy.J Orthop Res.2012;30:1963-1970.
[42]Ning L,Xu Z,Furuya N,et al.Perlecan inhibits autophagy to maintain muscle homeostasis in mouse soleus muscle.Matrix Biology.2015;48:26-35.
[43]Ulbricht A,Eppler FJ,Tapia VE,et al.Cellular mechanotransduction relies on tension-induced and chaperone-assisted autophagy.Curr Biol.2013;23:430-435.
[44]Ulbricht A,Gehlert S,Leciejewski B,et al.Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle.Autophagy.2015;11:538-546.
[45]Chen HC,Fong TH,Hsu PW,et al.Multifaceted effects of rapamycin on functional recovery after spinal cord injury in rats through autophagy promotion,anti-inflammation,and neuroprotection.J Surg Res.2013;179:e203-e210.
[46]Chen Z,Fu Q,Shen B,et al.Enhanced p62 expression triggers concomitant autophagy and apoptosis in a rat chronic spinal cord compression model.Mol Med Rep.2014;9:2091-2096.
[47]Wang ZY,Lin JH,Muharram A,et al.Beclin-1-mediated autophagy protects spinal cord neurons against mechanical injury-induced apoptosis.Apoptosis.2014;19:933-945.
[48]Park Y,Liu C,Luo T,et al.Chaperone-Mediated Autophagy after Traumatic Brain Injury.J Neurotrauma.2015;2:1449-1457.
[49]Lien SC,Chang SF,Lee PL,et al.Mechanical regulation of cancer cell apoptosis and autophagy:roles of bone morphogenetic protein receptor,Smad1/5,and p38 MAPK.Biochim Biophys Acta.2013;1833:3124-3133.
[50]Chen H,Chen LY,Cheng BA,et al.Cyclic Mechanical Stretching Induces Autophagic Cell Death in Tenofibroblasts Through Activation of Prostaglandin E2 Production.Cell Physiol Biochem.2015;36:24-33.
[51]Li D,Yan T,Xu Z,et al.Spironolactone Promotes Autophagy via Inhibiting PI3K/AKT/m TOR Pathway and Reduce Adhesive Damage in Podocytes under Mechanical Stress.Biosci Rep.2016.
[52]Porter KM,Jeyabalan N,Liton PB.MTOR-independent induction of autophagy in trabecular meshwork cells subjected to biaxial stretch.Bba-Mol Cell Res.2014;1843:1054-1062.
[2]Periyasamy-Thandavan S,Jiang M,Schoenlein P,et al.Autophagy:molecular machinery,regulation,and implications for renal pathophysiology.Am J Physiol Renal Physiol.2009;297:F244-F256.
[3]Reggiori F.Membrane origin for autophagy.Curr Top Dev Biol.2006;74:1-30.
[4]Klionsky DJ,Emr SD.Autophagy as a regulated pathway of cellular degradation.Science.2000;290:1717-1721.
[5]Fang Y,Tan J,Zhang Q.Signaling pathways and mechanisms of hypoxia-induced autophagy in the animal cells.Cell Biol Int.2015;39:891-898.
[6]Meng XX,Yao M,Zhang XD,et al.ER stress-induced autophagy in melanoma.Clin Exp Pharmacol Physiol.2015;42:811-816.
[7]Lin WJ,Kuang HY.Oxidative stress induces autophagy in response to multiple noxious stimuli in retinal ganglion cells.Autophagy.2014;10:1692-1701.
[8]Liu J,Bi X,Chen T,et al.Shear stress regulates endothelial cell autophagy via redox regulation and Sirt1 expression.Cell Death Dis.2015;6:e1827.
[9]Zhu HX,Tannous P,Johnstone JL,et al.Cardiac autophagy is a maladaptive response to hemodynamic stress.JCli Invest.2007;117:1782-1793.
[10]Nakai A,Yamaguchi O,Takeda T,et al.The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress.Nat Med.2007;13:619-624.
[11]Ma KG,Shao ZW,Yang SH,et al.Autophagy is activated in compression-induced cell degeneration and is mediated by reactive oxygen species in nucleus pulposus cells exposed to compression.Osteoarthr Cartilage.2013;21:2030-2038.
[12]Rothermel BA,Hill JA.Autophagy in load-induced heart disease.Circ Res.2008;103:1363-1369.
[13]Depre C,Wang Q,Yan L,et al.Activation of the cardiac proteasome during pressure overload promotes ventricular hypertrophy.Circulation.2006;114:1821-1828.
[14]Tannous P,Zhu HX,Nemchenko A,et al.Intracellular Protein Aggregation Is a Proximal Trigger of Cardiomyocyte Autophagy.Circ Res.2008;117(24):3070-3078.
[15]Lin L,Tang CY,Xu JF,et al.Mechanical Stress Triggers Cardiomyocyte Autophagy through Angiotensin II Type 1Receptor-Mediated p38MAP Kinase Independently of Angiotensin II.Plos One.2014;9(2):e89629.
[16]Weng LQ,Zhang WB,Ye Y,et al.Aliskiren ameliorates pressure overload-induced heart hypertrophy and fibrosis in mice.Acta Pharmacol Sin.2014;35:1005-1014.
[17]Lin L,Liu XB,Xu JF,et al.High-density lipoprotein inhibits mechanical stress-induced cardiomyocyte autophagy and cardiac hypertrophy through angiotensin II type 1receptor-mediated PI3K/Akt pathway.J Cell Mol Med.2015;19:1929-1938.
[18]Fu L,Wei CC,Powell PC,et al.Volume overload induces autophagic degradation of procollagen in cardiac fibroblasts.J Mol Cell Cardiol.2015;89:241-250.
[19]Hariharan N,Ikeda Y,Hong C,et al.Autophagy Plays an Essential Role in Mediating Regression of Hypertrophy during Unloading of the Heart.Plos One.2013;8(1):e51632.
[20]Cao DJ,Jiang N,Blagg A,et al.Mechanical Unloading Activates Fox O3 to Trigger Bnip3-Dependent Cardiomyocyte Atrophy.J Am Heart Assoc.2013;2(2):e000016.
[21]Baskin KK,Rodriguez MR,Kansara S,et al.MAFbx/Atrogin-1is required for atrophic remodeling of the unloaded heart.J Mol Cell Cardiol.2014;72:168-176.
[22]Kassiotis C,Ballal K,Wellnitz K,et al.Markers of Autophagy Are Downregulated in Failing Human Heart After Mechanical Unloading.Circulation.2009;120:S191-S197.
[23]Hill JA.Autophagy in cardiac plasticity and disease.Pediatr Cardiol.2011;32:282-289.
[24]Hariharan N,Maejima Y,Nakae J,et al.Deacetylation of Fox O by Sirt1 Plays an Essential Role in Mediating Starvation-Induced Autophagy in Cardiac Myocytes.Circ Res.2010;107:1470-1482.
[25]Skurk C,Izumiya Y,Maatz H,et al.The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling.J Biol Chem.2005;280:20814-20823.
[26]Sandri M,Sandri C,Gilbert A,et al.Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1and cause skeletal muscle atrophy.Cell.2004;117:399-412.
[27]Mammucari C,Milan G,Romanello V,et al.Fox O3 controls autophagy in skeletal muscle in vivo.Cell Metab.2007;6:458-471.
[28]Zhang HF,Bosch-Marce M,Shimoda LA,et al.Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia.J Biol Chem.2008;283:10892-10903.
[29]Porrello ER,D'amore A,Curl CL,et al.Angiotensin II type 2receptor antagonizes angiotensin II type 1 receptor-mediated cardiomyocyte autophagy.Hypertension.2009;53:1032-1040.
[30]Yadav A,Vallabu S,Arora S,et al.ANG II promotes autophagy in podocytes.Am J Physiol Cell Physiol.2010;299C488-C496.
[31]Huang J,Sun W,Huang H,et al.mi R-34a modulates angiotensin II-induced myocardial hypertrophy by direct inhibition of ATG9A expression and autophagic activity.PLo S One.2014;9(4):e94382.
[32]Yue H,Li W,Desnoyer R,et al.Role of nuclear unphosphorylated STAT3 in angiotensin II type 1 receptorinduced cardiac hypertrophy.Cardiovasc Res.2010;85:90-99.
[33]Ramakrishnan P,Hecht BA,Pedersen DR,et al.Oxidant conditioning protects cartilage from mechanically induced damage.J Orthop Res.2010;28:914-920.
[34]Thomas CM,Fuller CJ,Whittles CE,et al.Chondrocyte death by apoptosis is associated with cartilage matrix degradation.Osteoarthr Cartilage.2007;15:27-34.
[35]Carames B,Taniguchi N,Seino D,et al.Mechanical Injury Suppresses Autophagy Regulators and Pharmacologic Activation of Autophagy Results in Chondroprotection.Arthritis Rheumus.2012;64:1182-192.
[36]Xu HG,Yu YF,Zheng Q,et al.Autophagy protects end plate chondrocytes from intermittent cyclic mechanical tension induced calcification.Bone.2014;66:232-239.
[37]Pan S.Molecular mechanisms responsible for the atheroprotective effects of laminar shear stress.Antioxid Redox Sign.2009;11:1669-1682.
[38]Guo FX,Li XH,Peng J,et al.Autophagy Regulates Vascular Endothelial Cell e NOS and ET-1 Expression Induced by Laminar Shear Stress in an Ex Vivo Perfused System.Ann Biomed Eng.2014;42:1978-1988.
[39]Ding Z,Liu S,Deng X,et al.Hemodynamic shear stress modulates endothelial cell autophagy:Role of LOX-1.Int J Cardiol.2015;184:86-95.
[40]Bharath LP,Mueller R,Li Y,et al.Impairment of autophagy in endothelial cells prevents shear-stress-induced increases in nitric oxide bioavailability.Can J Physiol Pharmacol.2014;92:605-612.
[41]Gumucio JP,Davis ME,Bradley JR,et al.Rotator cuff tear reduces muscle fiber specific force production and induces macrophage accumulation and autophagy.J Orthop Res.2012;30:1963-1970.
[42]Ning L,Xu Z,Furuya N,et al.Perlecan inhibits autophagy to maintain muscle homeostasis in mouse soleus muscle.Matrix Biology.2015;48:26-35.
[43]Ulbricht A,Eppler FJ,Tapia VE,et al.Cellular mechanotransduction relies on tension-induced and chaperone-assisted autophagy.Curr Biol.2013;23:430-435.
[44]Ulbricht A,Gehlert S,Leciejewski B,et al.Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle.Autophagy.2015;11:538-546.
[45]Chen HC,Fong TH,Hsu PW,et al.Multifaceted effects of rapamycin on functional recovery after spinal cord injury in rats through autophagy promotion,anti-inflammation,and neuroprotection.J Surg Res.2013;179:e203-e210.
[46]Chen Z,Fu Q,Shen B,et al.Enhanced p62 expression triggers concomitant autophagy and apoptosis in a rat chronic spinal cord compression model.Mol Med Rep.2014;9:2091-2096.
[47]Wang ZY,Lin JH,Muharram A,et al.Beclin-1-mediated autophagy protects spinal cord neurons against mechanical injury-induced apoptosis.Apoptosis.2014;19:933-945.
[48]Park Y,Liu C,Luo T,et al.Chaperone-Mediated Autophagy after Traumatic Brain Injury.J Neurotrauma.2015;2:1449-1457.
[49]Lien SC,Chang SF,Lee PL,et al.Mechanical regulation of cancer cell apoptosis and autophagy:roles of bone morphogenetic protein receptor,Smad1/5,and p38 MAPK.Biochim Biophys Acta.2013;1833:3124-3133.
[50]Chen H,Chen LY,Cheng BA,et al.Cyclic Mechanical Stretching Induces Autophagic Cell Death in Tenofibroblasts Through Activation of Prostaglandin E2 Production.Cell Physiol Biochem.2015;36:24-33.
[51]Li D,Yan T,Xu Z,et al.Spironolactone Promotes Autophagy via Inhibiting PI3K/AKT/m TOR Pathway and Reduce Adhesive Damage in Podocytes under Mechanical Stress.Biosci Rep.2016.
[52]Porter KM,Jeyabalan N,Liton PB.MTOR-independent induction of autophagy in trabecular meshwork cells subjected to biaxial stretch.Bba-Mol Cell Res.2014;1843:1054-1062.