Sequential changes of endoplasmic reticulum stress and apoptosis in myocardial fibrosis of diabetes mellitus-induced rats.
The endoplasmic reticulum (ER) is an organelle in which proteins form their appropriate structures. However, several of these proteins become unfolded or misfolded when exposed to stimuli, including hyperglycemia, oxidative stress, ischemia, disturbance of calcium homeostasis and overexpression of abnormal proteins, which activates ER stress and the unfolded protein response (UPR). To date, investigations have demonstrated that ER stress is important in diabetic myocardial fibrosis by inducing cardiac cell apoptosis. Therefore, in the present study, the polymerase chain reaction, western blotting analysis and tissue staining were performed to identify the changes in UPR signaling proteins and apoptotic proteins in diabetic rats at different time points, and to determine whether the myocardial fibrosis is associated with ER-stress-mediated apoptosis using a diabetes mellitus (DM) rat model. It was found that the upregulation of ER stress markers and apoptotic molecules developed over time. It was also demonstrated that anti‑apoptotic markers and proapoptotic markers were activated early following model establishment, and then decreased in months 4 and 5. The changes in myocardial fibrosis were found to accelerate in a time-dependent manner with apoptosis in the DM rats.
Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
Qiong
Q
Yang
Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
Huikuan
H
Gao
Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
Ruiqing
R
Dong
Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
Yong-Quan
YQ
Wu
D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D009202:Cardiomyopathies / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress; D005355:Fibrosis; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013318:Stroke Volume; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
D051702:Activating Transcription Factor 6; D015415:Biomarkers; D006360:Heat-Shock Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; D019892:eIF-2 Kinase; C497113:Atf6 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP