全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
PLOS ONE  2013 

Decreased Autophagy Contributes to Myocardial Dysfunction in Rats Subjected to Nonlethal Mechanical Trauma

DOI: 10.1371/journal.pone.0071400

Full-Text   Cite this paper   Add to My Lib

Abstract:

Autophagy is important in cells for removing damaged organelles, such as mitochondria. Insufficient autophagy plays a critical role in tissue injury and organ dysfunction under a variety of pathological conditions. However, the role of autophagy in nonlethal traumatic cardiac damage remains unclear. The aims of the present study were to investigate whether nonlethal mechanical trauma may result in the change of cardiomyocyte autophagy, and if so, to determine whether the changed myocardial autophagy may contribute to delayed cardiac dysfunction. Male adult rats were subjected to nonlethal traumatic injury, and cardiomyocyte autophagy, cardiac mitochondrial function, and cardiac function in isolated perfused hearts were detected. Direct mechanical traumatic injury was not observed in the heart within 24 h after trauma. However, cardiomyocyte autophagy gradually decreased and reached a minimal level 6 h after trauma. Cardiac mitochondrial dysfunction was observed by cardiac radionuclide imaging 6 h after trauma, and cardiac dysfunction was observed 24 h after trauma in the isolated perfused heart. These were reversed when autophagy was induced by administration of the autophagy inducer rapamycin 30 min before trauma. Our present study demonstrated for the first time that nonlethal traumatic injury caused decreased autophagy, and decreased autophagy may contribute to post-traumatic organ dysfunction. Though our study has some limitations, it strongly suggests that cardiac damage induced by nonlethal mechanical trauma can be detected by noninvasive radionuclide imaging, and induction of autophagy may be a novel strategy for reducing posttrauma multiple organ failure.

References

[1]  Phillips J (2008) Traumatic injury in the ‘human zoo’. In: Phillips J. Trauma, Repair and Recovery. Oxford City: Oxford University Press. 1–20.
[2]  He J, Gu D, Wu X, Reynolds K, Duan X, et al. (2005) Major causes of death among men and women in China. N Engl J Med 353: 1124–1134.
[3]  Wang LT, Cheng SM, Chang LW, Liu MY, Wu CP, et al. (2008) Acute myocardial infarction caused by occult coronary intimal dissection after a heel stomp: a case report. J Trauma 64: 824–826.
[4]  Yoon YW, Park S, Lee SH, Cho M, Hong B, et al. (2007) Post-traumatic myocardial infarction complicated with left ventricular aneurysm and pericardial effusion. J Trauma 63: E73–75.
[5]  Ismailov RM, Ness RB, Weiss HB, Lawrence BA, Miller TR (2005) Trauma associated with acute myocardial infarction in a multi-state hospitalized population. Int J Cardiol 105: 141–146.
[6]  Sinha AK, Agrawal RK, Singh A, Kumar R, Kumar S, et al. (2002) Acute myocardial infarction due to blunt chest trauma. Indian Heart J 54: 713–714.
[7]  Vasudevan AR, Kabinoff GS, Keltz TN, Gitler B (2003) Blunt chest trauma producing acute myocardial infarction in a rugby player. Lancet 362: 370.
[8]  Wei T, Wang L, Chen L, Wang C, Zeng C (2002) Acute myocardial infarction and congestive heart failure following a blunt chest trauma. Heart Vessels 17: 77–79.
[9]  Shin IW, Jang IS, Lee SH, Baik JS, Park KE, et al. (2010) Propofol has delayed myocardial protective effects after a regional ischemia/reperfusion injury in an in vivo rat heart model. Korean J Anesthesiol 58: 378–382.
[10]  Abbate A, Biondi-Zoccai GG, Baldi A (2002) Pathophysiologic role of myocardial apoptosis in post-infarction left ventricular remodeling. J Cell Physiol 193: 145–153.
[11]  Chatterjee S, Bish LT, Jayasankar V, Stewart AS, Woo YJ, et al. (2003) Blocking the development of postischemic cardiomyopathy with viral gene transfer of the apoptosis repressor with caspase recruitment domain. J Thorac Cardiovasc Surg 125: 1461–1469.
[12]  Miao W, Luo Z, Kitsis RN, Walsh K (2000) Intracoronary, adenovirus-mediated Akt gene transfer in heart limits infarct size following ischemia-reperfusion injury in vivo. J Mol Cell Cardiol 32: 2397–2402.
[13]  Mocanu MM, Baxter GF, Yellon DM (2000) Caspase inhibition and limitation of myocardial infarct size: protection against lethal reperfusion injury. Br J Pharmacol 130: 197–200.
[14]  Tao L, Liu HR, Gao F, Qu Y, Christopher TA, et al. (2005) Mechanical traumatic injury without circulatory shock causes cardiomyocyte apoptosis: role of reactive nitrogen and reactive oxygen species. Am J Physiol Heart Circ Physiol 288: H2811–2818.
[15]  Sala-Mercado JA, Wider J, Undyala VV, Jahania S, Yoo W, et al. (2010) Profound Cardioprotection With Chloramphenicol Succinate in the Swine Model of Myocardial Ischemia-Reperfusion Injury. Circulation 122: S179–184.
[16]  Ravikumar B, Sarkar S, Davies JE, Futter M, Garcia-Arencibia M, et al. (2010) Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev 90: 1383–1435.
[17]  Augustine NKC, Stefan WR, Beth L (2013) Autophagy in human health and disease. N Engl J Med 368: 651–662.
[18]  Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132: 27–42.
[19]  Shintani T, Klionsky DJ (2004) Autophagy in health and disease: a double-edged sword. Science 306: 990–995.
[20]  Mizushima N, Levine B, Cuervo AM, Klionsky DJ (2008) Autophagy fights disease through cellular self-digestion. Nature 451: 1069–1075.
[21]  Cao Y, Klionsky DJ (2007) Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell Res 17: 839–849.
[22]  Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, et al. (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19: 5720–5728.
[23]  Sou YS, Tanida I, Komatsu M, Ueno T, Kominami E (2006) Phosphatidylserine in addition to phosphatidylethanolamine is an in vitro target of the mammalian Atg8 modifiers, LC3, GABARAP, and GATE-16. J Biol Chem 281: 3017–3024.
[24]  Tanida I, Ueno T, Kominami E (2004) LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol 36: 2503–2518.
[25]  Luo CL, Li BX, Li QQ, Chen XP, Sun YX, et al. (2011) Autophagy is involved in traumatic brain injury-induced cell death and contributes to functional outcome deficits in mice. Neuroscience 184: 54–63.
[26]  Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, et al. (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19: 5720–5728.
[27]  Kang R, Zeh HJ, Lotze MT, Tang D (2011) The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ 18: 571–580.
[28]  Yan L, Vatner DE, Kim SJ, Ge H, Masurekar M, et al. (2005) Autophagy in chronically ischemic myocardium. Proc Natl Acad Sci USA 102: 13807–13812.
[29]  Takemura G, Miyata S, Kawase Y, Okada H, Maruyama R, et al. (2006) Autophagic degeneration and death of cardiomyocytes in heart failure. Autophagy 2: 212–214.
[30]  Hein S, Arnon E, Kostin S, Sch?nburg M, Els?sser A, et al. (2003) Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation 107: 984–991.
[31]  Gustafsson AB, Gottlieb RA (2009) Autophagy in ischemic heart disease. Circ Res 104: 150–158.
[32]  Kim I, Rodriguez-Enriquez S, Lemasters JJ (2007) Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys 462: 245–253.
[33]  Schweers RL. Zhang J. Randall MS. Loyd MR. Li W, et al. (2007) NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci U S A 104: 19500–19505.
[34]  Levine B, Yuan J (2005) Autophagy in cell death: an innocent convict. J Clin Invest 115: 2679–2688.
[35]  Liu Z, Jonson G, Beju D, Okada RO (2001) Detection of myocardial viability in ischemic reperfused rat hearts by Tc-99m sestamibi kinetics. J Nucl Cardiol 8: 677–686.
[36]  Matsuo S, Nakae I, Tsutamoto T, Okamoto N, Horie M (2007) A novel clinical indicator using Tc-99m sestamibi for evaluating cardiac mitochondrial function in patients with cardiomyopathies. J Nucl Cardiol 14: 215–220.
[37]  Wu L, Feng Z, Cui S, Hou K, Tang L, et al. (2013) Rapamycin Upregulates Autophagy by Inhibiting the mTOR-ULK1 Pathway, Resulting in Reduced Podocyte Injury. PLoS One 8: e63799.
[38]  Tekirdag KA, Korkmaz G, Ozturk DG, Agami R, Gozuacik D (2013) MIR181A regulates starvation- and rapamycin-induced autophagy through targeting of ATG5. Autophagy 9: 374–385.
[39]  Huang H, Kang R, Wang J, Luo G, Yang W, et al. (2013) Hepatitis C virus inhibits AKT-tuberous sclerosis complex (TSC), the mechanistic target of rapamycin (MTOR) pathway, through endoplasmic reticulum stress to induce autophagy. Autophagy 9: 1751–195.
[40]  Regueira T, Andresen M, Djafarzadeh S (2009) Mitochondrial dysfunction during sepsis, impact and possible regulating role of hypoxia-inducible factor-1alpha. Med Intensiva 33: 385–392.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133