title: Endoplasmic reticulum stress response in spontaneously hypertensive rats is affected by myocardial ischemia reperfusion injury.
abstract: Cell apoptosis induced by endoplasmic reticulum (ER) stress appears to be one of the main causes of myocardial necrosis following myocardial ischemia/reperfusion (MI/R). The C/EBP homologous protein (CHOP) pathway is the main pathway through which apoptosis is induced during ER stress. Glucose-regulated protein 78 (GRP78) is an important protein involved in the CHOP pathway. The present study investigated the hypothesis that MI/R activates the CHOP pathway through signaling via a pathway involving PKR-like ER kinase (PERK), α-subunit of eukaryotic initiation factor 2 (eIF2α) and activating transcription factor 2 (ATF2). Immunohistochemical staining of the heart tissues from spontaneously hypersensitive rats indicated that MI/R injury increases CHOP and GPR78 protein expression levels. To further analyze the mechanism by which MI/R injury induces apoptosis by ER stress, the expression levels of five marker proteins involved in the hypothetical PERK-eIF2α-ATF2 pathway were detected, namely PERK, phosphorylated PERK (P-PERK), eIF2α, phosphorylated eIF2α (P-eIF2α) and ATF2. An increase in the collective expression levels of these proteins would indicate that apoptosis was induced by this signaling pathway. In addition, the study also explored whether hypertension affects the signaling pathway of MI/R-induced myocardial apoptosis by treating spontaneously hypertensive rats (SHRs) with captopril (an effective drug used to treat hypertension). Rats treated with captopril experienced a reduction in blood pressure to normal levels, but no marked differences in the expression levels of the tested proteins or in MI/R injury severity compared with those in untreated rats. These results suggest that MI/R activates the CHOP pathway during ER stress by activating the PERK-eIF2α-ATF2 pathway and that hypertension does not affect this signaling pathway.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China ; Department of Emergency and ICU, Suzhou Municipal Hospital (East Area), Suzhou, Jiangsu 215001, P.R. China.
authors.forename: Xiao-Fu
authors.initials: XF
authors.lastname: Guo
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Yang
keywords: PKR-like endoplasmic reticulum kinase; activating transcription factor 2; endoplasmic reticulum; glucose-regulated protein 78; myocardial necrosis; α-subunit of eukaryotic initiation factor 2