Calreticulin induces delayed cardioprotection through mitogen-activated protein kinases.
Hypoxic preconditioning (HPC) attenuates tissue injury caused by ischemia/reperfusion. The protective mechanisms of HPC involve up-regulation of the protective proteins and mitigation of cellular calcium overload. Calreticulin (CRT), a Ca(2+)-binding chaperone, plays an important role in regulating calcium homeostasis and folding of proteins. The role of CRT in cardioprotection of HPC and the pathways determining CRT expression during HPC are not clear. In this work, 2-DE and MALDI-MS were employed to analyze CRT differential expression in cardiomyocytes subjected to transient hypoxia. Western blotting analysis was used to detect the CRT expression and activities of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun NH(2)-terminal kinase (JNK) in myocardium subjected to ischemia with and without HPC and sham operation. The hearts from HPC group were more resistant to sustained ischemia and had much stronger phosphorylation of p38 MAPK, with a reduced phosphorylation of JNK, than controls. The CRT expression was positively correlated with the phosphorylation of p38 MAPK and negatively correlated with the level of JNK phosphorylation. Furthermore, inhibition of the p38 MAPK with SB202190 abolished, while inhibition of the JNK with SP600125 enhanced the CRT up-regulation in cardiomyocytes induced by HPC. The results indicate that HPC up-regulates CRT expression through the MAPK signaling pathways.
Liu
Xiuhua
X
Department of Pathophysiology, PLA General Hospital, Beijing 100853, China. xiuhualiu98@yahoo.com.cn
Xu
Feifei
F
Fu
Yan
Y
Liu
Fengying
F
Sun
Sheng
S
Wu
Xudong
X
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D037282:Calreticulin / Q000502:physiology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D037282:Calreticulin; D016328:NF-kappa B; D020928:Mitogen-Activated Protein Kinases