Endoplasmic Reticulum Stress and Mitochondrial Damage in Rat Cardiomyocytes after Acute Myocardial Infarction
Abstract
To study the alterations of endoplasmic reticulum (ER) stress and mitochondrial damage after acute myocardial infarction (AMI). Methods A total of 40 SD rats were used in this study and 32 of them were subjected to AMI by ligation of left anterior descending artery. The rats were sacrificed and the heart tissues were collected after 1 h, 2 h, 4 h and 6 h of AMI (n=8 per group). The mRNA levels of activating transcription factor 6 alpha (ATF6) and immunoglobulin heavy chain binding potein (BiP), as well as the expression of mitochondrial DNA (mtDNA) in cytoplasm were detected by RT-PCR. The ATP levels in the cardiomyocytes were detected by a commercial ATP assay kit. Results The mRNA levels of ATF6 and BiP were significantly increased after 1 h of AMI, which were maintained at high level from 2 h of AMI to the end of the experiment (P<0.05). The ATP concentrations in the cardiomyocytes were significantly elevated after 1 h of AMI but remarkably decreased after 4 h and 6 h of AMI (P<0.05). The release of mtDNA in cytoplasm was significantly increased after 2 h of AMI, followed by further elevations at 4 h and 6 h after AMI (P<0.05). Conclusion Mitochondrial damage is secondary to ER stress in AMI.
Keywords: Acute myocardial infarction, Endoplasmic reticulum stress, Mitochondrial damage, Myocardial protection
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MENEES D S, PETERSON E D, WANG Y, et al. Door-to-balloon time and mortality among patients undergoing primary PCI. N Engl J Med, 2013,369(10): 901–909.
LEVINE G N, BATES E R, BLANKENSHIP J C, et al. 2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: an update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation,2016,133(11): 1135–1147.
WEI C, WANG Y, LI M, et al. Spermine inhibits endoplasmic reticulum stress-induced apoptosis: a new strategy to prevent cardiomyocyte apoptosis. Cell Physiol Biochem,2016,38(2): 531–544.
YU L, LI S, TANG X, et al. Diallyl trisulfide ameliorates myocardial ischemia-reperfusion injury by reducing oxidative stress and endoplasmic reticulum stress-mediated apoptosis in type 1 diabetic rats: role of SIRT1 activation. Apoptosis,2017,22(7): 942–954.
YANG Q, WEN L, MENG Z, et al. Blockage of endoplasmic reticulum stress attenuates nilotinib-induced cardiotoxicity by inhibition of the Akt-GSK3beta-Nox4 signaling. Eur J Pharmacol,2018,822: 85–94.
AKHNOKH M K, YANG F H, SAMOKHVALOV V, et al. Inhibition of soluble epoxide hydrolase limits mitochondrial damage and preserves function following ischemic injury. Front Pharmacol, 2016, 7: 133[2019-10-13]. https://doi.org/10.3389/fphar.2016.00133.
ERTRACHT O, MALKA A, ATAR S, et al. The mitochondria as a target for cardioprotection in acute myocardial ischemia. Pharmacol Ther, 2014,142(1): 33–40.
YANG J, BROWN M E, ZHANG H, et al. High-throughput screening identifies microRNAs that target Nox2 and improve function after acute myocardial infarction. Am J Physiol Heart Circ Physiol,2017,312(5): H1002–H1012.
ZOU J, FEI Q, XIAO H, et al. VEGF-A promotes angiogenesis after acute myocardial infarction through increasing ROS production and enhancing ER stress-mediated autophagy. J Cell Physiol,2019,234(10): 17690–17703.
WIRES E S, HENDERSON M J, YAN X, et al. Longitudinal monitoring of Gaussia and nano luciferase activities to concurrently assess ER calcium homeostasis and ER stress in vivo. PLoS One, 2017, 12(4): e0175481 [2019-10-13]. https://doi.org/10.1371/journal.pone.0175481.
CASAS C. GRP78 at the centre of the stage in cancer and neuroprotection. Front Neurosci, 2017, 11: 177[2019-10-13]. https://www. ncbi.nlm.nih.gov/pmc/articles/PMC5380735/. doi: 10.3389/fnins.2017.00177.
WANG S, WANG Z, FAN Q, et al. Ginkgolide K protects the heart against endoplasmic reticulum stress injury by activating the inositol-requiring enzyme 1alpha/X box-binding protein-1 pathway. Br J Pharmacol,2016,173(15): 2402–2418.
SHI Z Y, LIU Y, DONG L, et al. Cortistatin improves cardiac function after acute myocardial infarction in rats by suppressing myocardial apoptosis and endoplasmic reticulum stress. J Cardiovasc Pharmacol Ther,2017,22(1): 83–93.
LIU M, XUE M, WANG X R, et al. Panax quinquefolium saponin attenuates cardiomyocyte apoptosis induced by thapsigargin through inhibition of endoplasmic reticulum stress. J Geriatr Cardiol,2015,12(5): 540–546.
CICEK F A, TOY A, TUNCAY E, et al. Beta-blocker timolol alleviates hyperglycemia-induced cardiac damage via inhibition of endoplasmic reticulum stress. J Bioenerg Biomembr,2014,46(5): 377–387.
JIN J K, BLACKWOOD E A, AZIZI K, et al. ATF6 decreases myocardial ischemia/reperfusion damage and links ER Stress and oxidative stress signaling pathways in the heart. Circ Res,2017,120(5): 862–875.
WIERSMA M, MEIJERING R A M, QI X Y, et al. Endoplasmic reticulum stress is associated with autophagy and cardiomyocyte remodeling in experimental and human atrial fibrillation. J Am Heart Assoc, 2017, 6(10): pii: e006458[2019-10-13]. https://doi.org/ 10.1161/JAHA.117.006458.
JENDRACH M, MAI S, POHL S, et al. Short- and long-term alterations of mitochondrial morphology, dynamics and mtDNA after transient oxidative stress. Mitochondrion,2008,8(4): 293–304.
WANG K, LIU C Y, ZHANG X J, et al. miR-361-regulated prohibitin inhibits mitochondrial fission and apoptosis and protects heart from ischemia injury. Cell Death Differ,2015,22(6): 1058–1068.
MARENZI G, COSENTINO N, BOEDDINGHAUS J, et al. Diagnostic and prognostic utility of circulating cytochrome c in acute myocardial infarction. Circ Res,2016,119(12): 1339–1346.
QIN C, LIU R, GU J, et al. Variation of perioperative plasma mitochondrial DNA correlate with peak inflammatory cytokines caused by cardiac surgery with cardiopulmonary bypass. J Cardiothorac Surg, 2015, 10: 85 [2019-10-13]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479323/. doi: 10.1186/s13019-015-0298-6.
QIN C, GU J, LIU R, et al. Release of mitochondrial DNA correlates with peak inflammatory cytokines in patients with acute myocardial infarction. Anatol J Cardiol,2017,17(3): 224–228.
KIM S H, KIM K Y, YU S N, et al. Silibinin induces mitochondrial NOX4-mediated endoplasmic reticulum stress response and its subsequent apoptosis. BMC Cancer, 2016, 16: 452[2010-10-13]. https://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2516-6. doi: 10.1186/s12885-016-2516-6.
KEMTER E, FROHLICH T, ARNOLD G J, et al. Mitochondrial dysregulation secondary to endoplasmic reticulum stress in autosomal dominant tubulointerstitial kidney disease-UMOD (ADTKD-UMOD). Sci Rep, 2017, 7: 42970[2010-10-13]. https://www.nature.com/articles/srep42970. doi: 10.1038/srep42970.
DENIAUD A, SHARAF EL DEIN O, MAILLIER E, et al. Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis. Oncogene,2008,27(3): 285–299.
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