TNF-α유발 심근비대세포의 AICAR 및 SIRT1 activator 처치후 Traf2와 SIRT1 발현 변화
Changes of Traf2 and SIRT1 Expression by AICAR and SIRT1 Activator in TNF-α -induced Cardiac Hypertrophy
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[PURPOSE] The study was aimed to identify the effects of Traf2 and SIRT1 on Akt aceytlation and autophagy in cardiac hypertrophy. [METHODS] We analyzed the effects of diet and exercise intervention on cardiac hypertrophy and the underlying mechanisms of TNF-α/Traf2/SIRT1 through Akt-FOXO pathway. [RESULTS] A significant up-regulation of Traf2 expression and down-regulation of SIRT1 were observed as the increase of TNF-α in cardiomyocytes. By the significant deacetylation of FOXO1 in 50 μM resveratrol treated group, we can suppose that FOXO1 is activated by SIRT1 in cardiomyocytes. Positive effects of exercise intervention remarkably inhibited the up-regulation of Traf2 expression and Akt acetylation in cardiac hypertrophy. However we could not confirm either a higher depression in Akt acetylation or the activation of FOXO1 by the SIRT1 activation. [CONCLUSION] The present study demonstrated that Traf2 served as an important mediator that enhanced cardiac hypertrophy by activating AKT pathway, and the positive effects of exercise training on the inhibition of Traf2 in cardiac hypertrophy.
Abstract
[PURPOSE] The study was aimed to identify the effects of Traf2 and SIRT1 on Akt aceytlation and autophagy in cardiac hypertrophy. [METHODS] We analyzed the effects of diet and exercise intervention on cardiac hypertrophy and the underlying mechanisms of TNF-α/Traf2/SIRT1 through Akt-FOXO pathway. [RESULTS] A significant up-regulation of Traf2 expression and down-regulation of SIRT1 were observed as the increase of TNF-α in cardiomyocytes. By the significant deacetylation of FOXO1 in 50 μM resveratrol treated group, we can suppose that FOXO1 is activated by SIRT1 in cardiomyocytes. Positive effects of exercise intervention remarkably inhibited the up-regulation of Traf2 expression and Akt acetylation in cardiac hypertrophy. However we could not confirm either a higher depression in Akt acetylation or the activation of FOXO1 by the SIRT1 activation. [CONCLUSION] The present study demonstrated that Traf2 served as an important mediator that enhanced cardiac hypertrophy by activating AKT pathway, and the positive effects of exercise training on the inhibition of Traf2 in cardiac hypertrophy.
참고문헌 (47)
- Achttien, R. J, "Exercise-based cardiac rehabilitation in patients with coronary heart disease: a practice guideline", Netherlands Heart Journal, 21, pp.429~438 (2013)
- Bijland, S, "Role of AMP activated protein kinase in adipose tissue metabolism and inflammation", Clinical Science (Lond), 124, pp.491~507 (2013)
- Blanc, A, "Synchronous acti\-vation of ERK 1", 2, p38mapk and PKB, International Journal of Molecular Medicine, pp.2003, 11[DOI]
- Börgeson, E, "AICAR ameliorates high-fat diet-associated pathophysiology in mouse and ex vivo models, independent of adiponectin", Diabetologia, 60, pp.729~739 (2017)
- Boudina, S, "Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes", Physiology (Bethesda), 21, pp.250~258 (2006)
- Ke Chen, "Vinexin-β protects against cardiac hypertrophy by blocking the Akt-dependent signalling pathway", Basic Research in Cardiology, 108(2), pp.338~ (2013), Springer Nature[DOI]
- Divakaran, V. G, "Tumor necrosis factor receptor-associated factor 2signaling provokes adverse cardiac remodeling in the adult mammalian heart", Circulation: Heart Failure, 6, pp.535~543 (2013)
- Dong, F., "Metallothionein prevents high-fat diet induced cardiac contractile dysfunction: role of peroxisome proliferator activated receptor gamma coactivator 1alpha and mitochondrial biogenesis", Diabetes, 56(9), pp.2201~2212 (2007)
- Donners, M. M. P. S, "The CD40–TRAF6 axis is the key regulator of the CD40", CD40L system in neointima formation and arterial remodeling, 2008, pp.111, 4596~4604
- Eckel, R. H, "Report of the National Heart, Lung, and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases Working Group on the pathophysiology of obesity-associated cardiovascular disease", Circulation, 105(24), pp.2923~2928 (2002)
- Ermolaeva, M. A, "Function of TRADD in tumor necrosis factor receptor 1signaling and in TRIF-dependent inflammatory responses", Nature Immunology, 9, pp.1037~1046 (2008)
- Fang, C. X, "Hypertrophic cardiomyopathy in high-fat diet-induced obesity: role of suppression of forkhead transcription factor and atrophy gene transcription", American Journal of Physiology: Heart Circulatory Physiology, 295(3), pp.H1206~H1215 (2008)
- Feuvray, D, "Diabetes-related metabolic perturbations in cardiac myocyte", Diabetes Metabolism, 34(Suppl. 1), pp.S3~S9 (2008)
- Ford, J, "Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and survival", Cancer Research, 65(22), pp.10457~10463 (2005)
- Franke, T. F, "PI3K", Akt and apoptosis:size matters, 2003, pp.22, 8983~8998
- Shérrira M. Garavelo, "Oral PTCTS (Particulated Transialidase) Removes Serum Microparticles and Decreases Inflammation in Atherosclerotic Plaques of Rabbits", Advances in Nanoparticles, 04(04), pp.107~115 (2015), Scientific Research Publishing, Inc,[DOI]
- Howitz, K. T, "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan", Nature, 425(6954), pp.191~196 (2003)
- Huang, Y, "Cardiac-specific Traf2 overexpression enhances cardiac hypertrophy through activating AKT", GSK3βsignaling, 2014, pp.536(2), 225~231
- Jono, H, "NF-kappaB is essential for induction of CYLD, the negative regulator of NF-kappaB: evidence for a novel inducible autoregulatory feedback pathway", Journal of Biological Chemistry, 279, pp.36171~36174 (2004)
- Kojima, K, "A role for SIRT1 in cell growth and chemoresistance in prostate cancer PC3and DU145 cells", Biochemical and Biophysical Research Communications, 373(3), pp.423~428 (2008)
- Levy, D, "Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study", New England Journal of Medicine, 322(22), pp.1561~1566 (1990)
- Leychenko, A, "Stretch-induced hypertrophy activates NFkB-mediated VEGF secretion in adult cardiomyocytes", PLoS One, 6, pp.e29055~ (2011)
- Li, J, "PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer", Science, 275(5308), pp.1943~1947 (1997)
- Li, S. Y, "Cardiac contractile dysfunction in Lep", Lep obesity is accompanied by NADPH oxidase activation, oxidative modification of sarco(endo)plasmic reticulum Ca2+-ATPase and myosin heavy chain isozyme switch, 2006, pp.49(6), 1434~1446
- Lima-Leopoldo, A. P, "Obesity induces upregulation of genes involved in myocardial Ca2+ handling", Brazilian Journal of Medical and Biological Research, 41(7), pp.615~620 (2008)
- Lin, C. H, "Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K", Akt signaling to improve the effects of exercise in elderly rat hearts, 2014, pp.36(5), 9705~
- Lowry, O. H, "Protein measurement with the folin ohenol reagent", Journal of Biological Chemistry, 193(1), pp.265~275 (1951)
- Lu, K, "Effects of high-intensity interval versus continuous moderate\_intensity aerobic exercise on apoptosis, oxidative stress and metabolism of the infarcted myocardium in a rat model", Molecular Medicine Report, 12, pp.2374~2382 (2015)
- Maillet, M, "Molecular basis of physiological heart growth: fundamental concepts and new players", Nature Reviews Molecular Cell Biology, 14, pp.38~48 (2013)
- Mammucari, C, "FoxO3controls autophagy in skeletal muscle in vivo", Cell Metabolism, 6(6), pp.458~471 (2007)
- Mark Christian C. Manio, "Combined pharmacological activation of AMPK and PPARδ potentiates the effects of exercise in trained mice", Physiological Reports, 4(5), pp.e12625~ (2016), Wiley[DOI]
- Nishida, K, "The role of autophagy in the heart", Cell Death and Differentiation, 16(1), pp.31~38 (2009)
- Oldridge, N, "Exercise-based cardiac rehabilitation in patients with coronary heart disease: meta-analysis outcomes revisited", Future Cardiology, 8, pp.729~751 (2012)
- Ouwens, D. M, "Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats", Diabetologia, 48(6), pp.1229~1237 (2005)
- Santos, M. H, "Previous exercise training increases levels of PPAR-α in long-term post-myocardial infarction in rats, which is correlated with better inflammatory response", Clinics, 71(3), pp.163~168 (2016)
- Santos, D. G, "Nuclear factor (NF) kappaB polymorphism is associated with heart function in patients with heart failure", BMC Medical Genetics, 11, pp.89~ (2010)
- Sengupta, A, "FoxO transcription factors promote autophagy in cardiomyocytes", Journal of Biological Chemistry, 284(41), pp.28319~28331 (2009)
- Shih, V. F, "A single NFkappaB system for both canonical and non-canonical signaling", Cell Research, 21, pp.86~102 (2011)
- Smeets, P. J, "Inflammatory pathways are activated during cardiomyocyte hypertrophy and attenuated by peroxisome proliferator-activated receptors PPARalpha and PPARdelta", Journal of Biological Chemistry, 283(43), pp.29109~29118 (2008)
- Sowers, J. R, "Obesity as a cardiovascular risk factor", American Journal of Medicine, 115(Suppl 8A), pp.37S~41S (2003)
- Sundaresan, N. R, "The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy", Scientific Signaling, 4(182), pp.ra46~ (2011)
- Thaik, C. M, "Interleukin-1 beta modulates the growth and phenotype of neonatal rat cardiac myocytes", Journal of Clinical Investigation, 96(2), pp.1093~1099 (1995)
- Turdi, S, "Deficiency in AMP-activated protein kinase exaggerates high fat diet-induced cardiac hypertrophy and contractile dysfunction", Journal of Molecular Cellular Cardiology, 50(4), pp.712~722 (2010)
- Yang, Z, "The Full Capacity of AICAR to Reduce Obesity-Induced Inflammation and Insulin Resistance Requires Myeloid SIRT1", Plos One, 7(11), pp.e49935~ (2012)
- Yokoyama, T, "Tumor necrosis factor-alpha provokes a hypertrophic growth response in adult cardiac myocytes", Circulation, 95(5), pp.1247~1252 (1997)
- Zhao, J, "FoxO3 coordinately activates protein degradation by the autophagic", lysosomal and proteasomal pathways in atrophying muscle cells, 2007, pp.6(6), 472~483
- Zhu, X, "Activation of Sirt1 by resveratrol inhibits TNF-α induced inflammation in fibroblasts", PLoS One, 6(11), pp.e27081~ (2011)