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Sex Differences in Ischemia/Reperfusion Injury: The Role of Mitochondrial Permeability Transition.

TitleSex Differences in Ischemia/Reperfusion Injury: The Role of Mitochondrial Permeability Transition.
Publication TypeJournal Article
Year of Publication2019
AuthorsFels JA, Manfredi G
JournalNeurochem Res
Date Published2019 Mar 12
ISSN1573-6903
Abstract

Brain and heart ischemia are among the leading causes of death and disability in both men and women, but there are significant sex differences in the incidence and severity of these diseases. Ca dysregulation in response to ischemia/reperfusion injury (I/RI) is a well-recognized pathogenic mechanism leading to the death of affected cells. Excess intracellular Ca causes mitochondrial matrix Ca overload that can result in mitochondrial permeability transition (MPT), which can have severe consequences for mitochondrial function and trigger cell death. Recent findings indicate that estrogens and their related receptors are involved in the regulation of MPT, suggesting that sex differences in I/RI could be linked to estrogen-dependent modulation of mitochondrial Ca. Here, we review the evidence supporting sex differences in I/RI and the role of estrogen and estrogen receptors in producing these differences, the involvement of mitochondrial Ca overload in disease pathogenesis, and the estrogen-dependent modulation of MPT that may contribute to sex differences.

DOI10.1007/s11064-019-02769-6
Alternate JournalNeurochem. Res.
PubMed ID30863968
Grant ListR01 NS095692 / NS / NINDS NIH HHS / United States
R01NS095692 / / National Institute of Neurological Disorders and Stroke /