J Gao1, L Zhang, W-L Wang, Q Ma, H-C Chu. 1. Department of Anesthesia, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. chuhaichenqd@126.com.
Abstract
OBJECTIVE: PUMA is a pro-apoptotic gene, which has been found to be critical to the pathogenesis during heart ischemia-reperfusion injury (IRI). We investigate whether anti-PUMA protect mice from acute heart failure. MATERIALS AND METHODS: Mice were subjected to 30 min ischemia and 24 hrs reperfusion in the presence or absence of anti-PUMA. Treated mice were evaluated for heart PUMA protein and mRNA expression, and apoptosis by terminal deoxy nucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: In mice, anti-PUMA post conditioning markedly reduced PUMA mRNA and protein expression in the heart 4-fold. Hearts from mice that received anti-PUMA had substantially fewer heart muscles apoptosis by TUNEL staining. Anti-PUMA post-conditioning greatly reduced infarct size to 14.4±3.7%, from 38.2±3.9% in the untreated I/R group. Furthermore, survival experiments revealed that more than 90% of control mice died from lethal I/R, whereas 20% of the anti-PUMA post-treated mice survived until the end of the 10-day observation period. CONCLUSIONS: This study confirms the importance of PUMA-mediated apoptosis in heart ischemia-reperfusion injury. Silencing PUMA by recombinant PUMA has therapeutic promise to limit ischemia-reperfusion injury.
OBJECTIVE:PUMA is a pro-apoptotic gene, which has been found to be critical to the pathogenesis during heart ischemia-reperfusion injury (IRI). We investigate whether anti-PUMA protect mice from acute heart failure. MATERIALS AND METHODS:Mice were subjected to 30 min ischemia and 24 hrs reperfusion in the presence or absence of anti-PUMA. Treated mice were evaluated for heart PUMA protein and mRNA expression, and apoptosis by terminal deoxy nucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: In mice, anti-PUMA post conditioning markedly reduced PUMA mRNA and protein expression in the heart 4-fold. Hearts from mice that received anti-PUMA had substantially fewer heart muscles apoptosis by TUNEL staining. Anti-PUMA post-conditioning greatly reduced infarct size to 14.4±3.7%, from 38.2±3.9% in the untreated I/R group. Furthermore, survival experiments revealed that more than 90% of control mice died from lethal I/R, whereas 20% of the anti-PUMA post-treated mice survived until the end of the 10-day observation period. CONCLUSIONS: This study confirms the importance of PUMA-mediated apoptosis in heart ischemia-reperfusion injury. Silencing PUMA by recombinant PUMA has therapeutic promise to limit ischemia-reperfusion injury.