Estrogen prevents cardiomyocyte apoptosis through inhibition of reactive oxygen species and differential regulation of p38 kinase isoforms - PubMed (original) (raw)
Comparative Study
. 2006 Mar 10;281(10):6760-7.
doi: 10.1074/jbc.M511024200. Epub 2005 Dec 30.
Affiliations
- PMID: 16407188
- DOI: 10.1074/jbc.M511024200
Free article
Comparative Study
Estrogen prevents cardiomyocyte apoptosis through inhibition of reactive oxygen species and differential regulation of p38 kinase isoforms
Jin Kyung Kim et al. J Biol Chem. 2006.
Free article
Abstract
From human and animal studies, estrogen is known to protect the myocardium from an ischemic insult. However, there is limited knowledge regarding mechanisms by which estrogen directly protects cardiomyocytes. In this report, we employed an in vitro model, in which cultured rat cardiomyocytes underwent prolonged hypoxia followed by reoxygenation (H/R), to study the cardioprotective mechanism of estrogen. 17-beta-estradiol (E2) acting via estrogen receptors inhibited H/R-induced apoptosis of cardiomyocytes. Mitochondrial reactive oxygen species (ROS) generated from H/R activated p38alpha MAPK, and inhibition of p38alpha with SB203580 significantly prevented H/R-induced cell death. E2 suppressed ROS formation and p38alpha activation by H/R and concomitantly augmented the activity of p38beta. Unlike p38alpha, p38beta was little affected by H/R. Dominant negative p38beta protein expression decreased E2-mediated cardiomyocyte survival and ROS suppression during H/R stress. The prosurvival signaling molecule, phosphoinositol-3 kinase (PI3K), has previously been linked to cell survival following ischemia-reperfusion injury. Here, E2-activated PI3K was found to inhibit ROS generated from H/R injury, leading to inhibition of downstream p38alpha. We further linked these signaling pathways in that p38beta was activated by E2 stimulation of PI3K. Thus, E2 differentially modulated two major isoforms of p38, leading to cardiomyocyte survival. This was achieved by signaling through PI3K, integrating cell survival mediators.
Similar articles
- Oestrogen prevents cardiomyocyte apoptosis by suppressing p38α-mediated activation of p53 and by down-regulating p53 inhibition on p38β.
Liu H, Pedram A, Kim JK. Liu H, et al. Cardiovasc Res. 2011 Jan 1;89(1):119-28. doi: 10.1093/cvr/cvq265. Epub 2010 Aug 19. Cardiovasc Res. 2011. PMID: 20724307 Free PMC article. - Mitochondrial p38β and manganese superoxide dismutase interaction mediated by estrogen in cardiomyocytes.
Liu H, Yanamandala M, Lee TC, Kim JK. Liu H, et al. PLoS One. 2014 Jan 22;9(1):e85272. doi: 10.1371/journal.pone.0085272. eCollection 2014. PLoS One. 2014. PMID: 24465521 Free PMC article. - Estrogen Protects the Female Heart from Ischemia/Reperfusion Injury through Manganese Superoxide Dismutase Phosphorylation by Mitochondrial p38β at Threonine 79 and Serine 106.
Luo T, Liu H, Kim JK. Luo T, et al. PLoS One. 2016 Dec 8;11(12):e0167761. doi: 10.1371/journal.pone.0167761. eCollection 2016. PLoS One. 2016. PMID: 27930699 Free PMC article. - Attenuation of mitochondrial and nuclear p38α signaling: a novel mechanism of estrogen neuroprotection in cerebral ischemia.
Han D, Scott EL, Dong Y, Raz L, Wang R, Zhang Q. Han D, et al. Mol Cell Endocrinol. 2015 Jan 15;400:21-31. doi: 10.1016/j.mce.2014.11.010. Epub 2014 Nov 25. Mol Cell Endocrinol. 2015. PMID: 25462588 - p38 MAPK Pathway in the Heart: New Insights in Health and Disease.
Romero-Becerra R, Santamans AM, Folgueira C, Sabio G. Romero-Becerra R, et al. Int J Mol Sci. 2020 Oct 8;21(19):7412. doi: 10.3390/ijms21197412. Int J Mol Sci. 2020. PMID: 33049962 Free PMC article. Review.
Cited by
- Sex difference in human diseases: mechanistic insights and clinical implications.
Shi Y, Ma J, Li S, Liu C, Liu Y, Chen J, Liu N, Liu S, Huang H. Shi Y, et al. Signal Transduct Target Ther. 2024 Sep 10;9(1):238. doi: 10.1038/s41392-024-01929-7. Signal Transduct Target Ther. 2024. PMID: 39256355 Free PMC article. Review. - Primary Prevention of Cardiovascular Disease in Women.
Shahid I, Avenatti E, Titus A, Al-Kindi S, Nasir K. Shahid I, et al. Methodist Debakey Cardiovasc J. 2024 Mar 14;20(2):94-106. doi: 10.14797/mdcvj.1313. eCollection 2024. Methodist Debakey Cardiovasc J. 2024. PMID: 38495667 Free PMC article. Review. - Computational screen for sex-specific drug effects in a cardiac fibroblast signaling network model.
Watts KM, Nichols W, Richardson WJ. Watts KM, et al. Sci Rep. 2023 Oct 10;13(1):17068. doi: 10.1038/s41598-023-44440-9. Sci Rep. 2023. PMID: 37816826 Free PMC article. - Beyond hot flashes: Exploring the role of estrogen therapy in postmenopausal women for myocardial infarction prevention and recovery.
Choradia A, Bai K, Soni S, Nguyen N, Adhikari S, Kaur Rahul D, Gupta R. Choradia A, et al. Biomol Biomed. 2024 Jan 3;24(1):4-13. doi: 10.17305/bb.2023.9535. Biomol Biomed. 2024. PMID: 37650466 Free PMC article. Review. - The Role of P53 in Myocardial Ischemia-Reperfusion Injury.
Zhu XZ, Qiu Z, Lei SQ, Leng Y, Li WY, Xia ZY. Zhu XZ, et al. Cardiovasc Drugs Ther. 2023 Jun 30. doi: 10.1007/s10557-023-07480-x. Online ahead of print. Cardiovasc Drugs Ther. 2023. PMID: 37389674 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources