Sex differences play a role in cardiac endoplasmic reticulum stress (ERS) and ERS-initiated apoptosis induced by pressure overload and thapsigargin

Flori R. Sari, Kenichi Watanabe, Bambang Widyantoro, Rajarajan A. Thandavarayan, Meilei Harima, Makoto Kodama, Yoshifusa Aizawa

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Excessive endoplasmic reticulum stress (ERS) triggers myocardial apoptosis. Sex differences appear to be an important determinant in the occurrence of stress and apoptosis through many pathways, but the roles of sex differences in the cardiac ERS and ERS-initiated apoptosis are largely unknown. In the present study, we investigated the in vivo role of sex differences in the cardiac ERS and apoptosis elicited by ascending aortic banding surgery or thapsigargin (Thap) injection using male and female C57BL/6 JAX mice. The surgery significantly increased the expression levels of cardiac glucose-regulated protein (GRP)78 and CCAAT/enhancer binding protein homology protein (CHOP) protein, increased the myocardial apoptosis and decreased the sarcoplasmic reticulum Ca 2+-ATPase isoform (SERCA)2 immunoreactivity in the male mice relative to female mice. Furthermore, during ERS induction using Thap, myocardial apoptosis and the expression levels of cardiac GRP78, inositol-requiring enzyme (Ire)1α and tumor necrosis factor receptor-associated factor (TRAF)2 were significantly increased in male mice relative to female mice. Sex differences significantly affected the above results. Our data suggest that sex differences affected the response of myocardial tissues in dealing with cardiac ERS and further result of ERS, apoptosis, at least in part through the regulation of SERCA2, CHOP, Ire1α and TRAF2.

Original languageEnglish (US)
Pages (from-to)281-290
Number of pages10
JournalCardiovascular Pathology
Volume20
Issue number5
DOIs
StatePublished - Sep 2011

Keywords

  • Apoptosis
  • Ascending aortic banding
  • Endoplasmic reticulum stress
  • Sex differences
  • Thapsigargin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cardiology and Cardiovascular Medicine

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