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Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents
Opioids reduce injury from myocardial ischemia-reperfusion in humans. In experimental models, this mechanism involves GSK3β inhibition. HSP90 regulates mitochondrial protein import, with GSK3β inhibition increasing HSP90 mitochondrial content. Therefore, we determined whether morphine-induced cardio...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564588/ https://www.ncbi.nlm.nih.gov/pubmed/26413502 http://dx.doi.org/10.1155/2015/129612 |
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author | Small, Bryce A. Lu, Yao Hsu, Anna K. Gross, Garrett J. Gross, Eric R. |
author_facet | Small, Bryce A. Lu, Yao Hsu, Anna K. Gross, Garrett J. Gross, Eric R. |
author_sort | Small, Bryce A. |
collection | PubMed |
description | Opioids reduce injury from myocardial ischemia-reperfusion in humans. In experimental models, this mechanism involves GSK3β inhibition. HSP90 regulates mitochondrial protein import, with GSK3β inhibition increasing HSP90 mitochondrial content. Therefore, we determined whether morphine-induced cardioprotection is mediated by HSP90 and if the protective effect is downstream of GSK3β inhibition. Male Sprague-Dawley rats, aged 8–10 weeks, were subjected to an in vivo myocardial ischemia-reperfusion injury protocol involving 30 minutes of ischemia followed by 2 hours of reperfusion. Hemodynamics were continually monitored and myocardial infarct size determined. Rats received morphine (0.3 mg/kg), the GSK3β inhibitor, SB216763 (0.6 mg/kg), or saline, 10 minutes prior to ischemia. Some rats received selective HSP90 inhibitors, radicicol (0.3 mg/kg), or deoxyspergualin (DSG, 0.6 mg/kg) alone or 5 minutes prior to morphine or SB216763. Morphine reduced myocardial infarct size when compared to control (42 ± 2% versus 60 ± 1%). This protection was abolished by prior treatment of radicicol or DSG (59 ± 1%, 56 ± 2%). GSK3β inhibition also reduced myocardial infarct size (41 ± 2%) with HSP90 inhibition by radicicol or DSG partially inhibiting SB216763-induced infarct size reduction (54 ± 3%, 47 ± 1%, resp.). These data suggest that opioid-induced cardioprotection is mediated by HSP90. Part of this protection afforded by HSP90 is downstream of GSK3β, potentially via the HSP-TOM mitochondrial import pathway. |
format | Online Article Text |
id | pubmed-4564588 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-45645882015-09-27 Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents Small, Bryce A. Lu, Yao Hsu, Anna K. Gross, Garrett J. Gross, Eric R. Biomed Res Int Research Article Opioids reduce injury from myocardial ischemia-reperfusion in humans. In experimental models, this mechanism involves GSK3β inhibition. HSP90 regulates mitochondrial protein import, with GSK3β inhibition increasing HSP90 mitochondrial content. Therefore, we determined whether morphine-induced cardioprotection is mediated by HSP90 and if the protective effect is downstream of GSK3β inhibition. Male Sprague-Dawley rats, aged 8–10 weeks, were subjected to an in vivo myocardial ischemia-reperfusion injury protocol involving 30 minutes of ischemia followed by 2 hours of reperfusion. Hemodynamics were continually monitored and myocardial infarct size determined. Rats received morphine (0.3 mg/kg), the GSK3β inhibitor, SB216763 (0.6 mg/kg), or saline, 10 minutes prior to ischemia. Some rats received selective HSP90 inhibitors, radicicol (0.3 mg/kg), or deoxyspergualin (DSG, 0.6 mg/kg) alone or 5 minutes prior to morphine or SB216763. Morphine reduced myocardial infarct size when compared to control (42 ± 2% versus 60 ± 1%). This protection was abolished by prior treatment of radicicol or DSG (59 ± 1%, 56 ± 2%). GSK3β inhibition also reduced myocardial infarct size (41 ± 2%) with HSP90 inhibition by radicicol or DSG partially inhibiting SB216763-induced infarct size reduction (54 ± 3%, 47 ± 1%, resp.). These data suggest that opioid-induced cardioprotection is mediated by HSP90. Part of this protection afforded by HSP90 is downstream of GSK3β, potentially via the HSP-TOM mitochondrial import pathway. Hindawi Publishing Corporation 2015 2015-08-27 /pmc/articles/PMC4564588/ /pubmed/26413502 http://dx.doi.org/10.1155/2015/129612 Text en Copyright © 2015 Bryce A. Small et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Small, Bryce A. Lu, Yao Hsu, Anna K. Gross, Garrett J. Gross, Eric R. Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents |
title | Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents |
title_full | Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents |
title_fullStr | Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents |
title_full_unstemmed | Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents |
title_short | Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents |
title_sort | morphine reduces myocardial infarct size via heat shock protein 90 in rodents |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564588/ https://www.ncbi.nlm.nih.gov/pubmed/26413502 http://dx.doi.org/10.1155/2015/129612 |
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