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Mitochondrial Dysfunction Secondary to Endoplasmic Reticulum Stress in Acute Myocardial Ischemic Injury in Rats

BACKGROUND: The relationship between endoplasmic reticulum and mitochondria during acute myocardial ischemic injury is still unclear. Our study aimed to define the dynamics of endoplasmic reticulum stress and mitochondrial dysfunction during acute ischemic injury. MATERIAL/METHODS: A rat model of ac...

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Autores principales: Qin, Chaoyi, Wu, Xue-lin, Gu, Jun, Du, Dan, Guo, Yingqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261002/
https://www.ncbi.nlm.nih.gov/pubmed/32439834
http://dx.doi.org/10.12659/MSM.923124
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author Qin, Chaoyi
Wu, Xue-lin
Gu, Jun
Du, Dan
Guo, Yingqiang
author_facet Qin, Chaoyi
Wu, Xue-lin
Gu, Jun
Du, Dan
Guo, Yingqiang
author_sort Qin, Chaoyi
collection PubMed
description BACKGROUND: The relationship between endoplasmic reticulum and mitochondria during acute myocardial ischemic injury is still unclear. Our study aimed to define the dynamics of endoplasmic reticulum stress and mitochondrial dysfunction during acute ischemic injury. MATERIAL/METHODS: A rat model of acute myocardial infarction and hypoxic cardiomyocytes were used in this study. Groups were set at 0 hours, 1 hour, 2 hours, 4 hours, and 6 hours after ischemic injury for both in vivo and in vitro studies. ATF6 and GRP-78 were examined to indicate endoplasmic reticulum stress. Cellular ATP and cytosolic levels of mitochondrial DNA and cytochrome c were detected to evaluate mitochondrial dysfunction. Caspase-3 was used for apoptosis analysis. RESULT: Our results showed that both mRNA and protein levels of ATF6 and GRP-78 were elevated from 1 hour after ischemic injury in vivo and in vitro (P<0.05). However, ATP levels were increased at 2 hours after ischemic injury and significantly decreased from 4 hours after ischemic injury in vivo, while ATP level of cultured cardiomyocytes decreased remarkably from 2 hours after ischemic injury (P<0.05). Cytosolic mitochondrial DNA levels began to increase from 2 hours after ischemic injury (P<0.05). Cytosolic levels of cytochrome c increased from 4 hours after ischemic injury. Additionally, both mRNA and protein expressions of caspase-3 started to significantly elevate at 6 hours after ischemic injury (P<0.05). CONCLUSIONS: The present study suggested that mitochondrial dysfunction was secondary to endoplasmic reticulum stress, which provides a novel experimental foundation for further exploration of the detailed mechanism after ischemic injury, especially the interaction between endoplasmic reticulum and mitochondria.
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spelling pubmed-72610022020-06-01 Mitochondrial Dysfunction Secondary to Endoplasmic Reticulum Stress in Acute Myocardial Ischemic Injury in Rats Qin, Chaoyi Wu, Xue-lin Gu, Jun Du, Dan Guo, Yingqiang Med Sci Monit Animal Study BACKGROUND: The relationship between endoplasmic reticulum and mitochondria during acute myocardial ischemic injury is still unclear. Our study aimed to define the dynamics of endoplasmic reticulum stress and mitochondrial dysfunction during acute ischemic injury. MATERIAL/METHODS: A rat model of acute myocardial infarction and hypoxic cardiomyocytes were used in this study. Groups were set at 0 hours, 1 hour, 2 hours, 4 hours, and 6 hours after ischemic injury for both in vivo and in vitro studies. ATF6 and GRP-78 were examined to indicate endoplasmic reticulum stress. Cellular ATP and cytosolic levels of mitochondrial DNA and cytochrome c were detected to evaluate mitochondrial dysfunction. Caspase-3 was used for apoptosis analysis. RESULT: Our results showed that both mRNA and protein levels of ATF6 and GRP-78 were elevated from 1 hour after ischemic injury in vivo and in vitro (P<0.05). However, ATP levels were increased at 2 hours after ischemic injury and significantly decreased from 4 hours after ischemic injury in vivo, while ATP level of cultured cardiomyocytes decreased remarkably from 2 hours after ischemic injury (P<0.05). Cytosolic mitochondrial DNA levels began to increase from 2 hours after ischemic injury (P<0.05). Cytosolic levels of cytochrome c increased from 4 hours after ischemic injury. Additionally, both mRNA and protein expressions of caspase-3 started to significantly elevate at 6 hours after ischemic injury (P<0.05). CONCLUSIONS: The present study suggested that mitochondrial dysfunction was secondary to endoplasmic reticulum stress, which provides a novel experimental foundation for further exploration of the detailed mechanism after ischemic injury, especially the interaction between endoplasmic reticulum and mitochondria. International Scientific Literature, Inc. 2020-05-22 /pmc/articles/PMC7261002/ /pubmed/32439834 http://dx.doi.org/10.12659/MSM.923124 Text en © Med Sci Monit, 2020 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Animal Study
Qin, Chaoyi
Wu, Xue-lin
Gu, Jun
Du, Dan
Guo, Yingqiang
Mitochondrial Dysfunction Secondary to Endoplasmic Reticulum Stress in Acute Myocardial Ischemic Injury in Rats
title Mitochondrial Dysfunction Secondary to Endoplasmic Reticulum Stress in Acute Myocardial Ischemic Injury in Rats
title_full Mitochondrial Dysfunction Secondary to Endoplasmic Reticulum Stress in Acute Myocardial Ischemic Injury in Rats
title_fullStr Mitochondrial Dysfunction Secondary to Endoplasmic Reticulum Stress in Acute Myocardial Ischemic Injury in Rats
title_full_unstemmed Mitochondrial Dysfunction Secondary to Endoplasmic Reticulum Stress in Acute Myocardial Ischemic Injury in Rats
title_short Mitochondrial Dysfunction Secondary to Endoplasmic Reticulum Stress in Acute Myocardial Ischemic Injury in Rats
title_sort mitochondrial dysfunction secondary to endoplasmic reticulum stress in acute myocardial ischemic injury in rats
topic Animal Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261002/
https://www.ncbi.nlm.nih.gov/pubmed/32439834
http://dx.doi.org/10.12659/MSM.923124
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