Sex differences play a role in cardiac endoplasmic reticulum stress (ERS) and ERS-initiated apoptosis induced by pressure overload and thapsigargin.
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.
Sari
Flori R
FR
Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan.
Watanabe
Kenichi
K
Widyantoro
Bambang
B
Thandavarayan
Rajarajan A
RA
Harima
Meilei
M
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000503:physiopathology / Q000601:surgery; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D023081:CCAAT-Binding Factor / Q000378:metabolism; D004195:Disease Models, Animal; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006360:Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D011312:Pressure / Q000009:adverse effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000201:enzymology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D012737:Sex Factors; D019284:Thapsigargin / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D023081:CCAAT-Binding Factor; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D008565:Membrane Proteins; C499176:T2bp protein, mouse; D051742:Transcription Factor CHOP; D019284:Thapsigargin; C486556:Ern2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases