Burn-induced apoptosis of cardiomyocytes is survivin dependent and regulated by PI3K/Akt, p38 MAPK and ERK pathways
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Wei Cao ,Yan-Hua Xie , Xiao-Qiang Li , Xiao-Kai Zhang , Yue-Tao Chen , Rong Kang , Xi Chen , Shan Miao , Si-Wang Wang
- چاپ و سال / کشور: 2011
Description
Survivin belongs to the family of genes known as inhibitors of apoptosis, and although it has been implicated in the prevention of cancer, its potential role in burn-induced cardiac injury is unknown. In this study, we investigated the effects of survivin blockade on burn-induced cardiac apoptosis. Using a standardized Sprague-Dawley rat model of third-degree burn injury over 40% of total body surface area, apoptosis was measured in vivo followed by in vitro assessment of burn serum-stimulated cardiomyocytes. Based on the Western blot analyses, real-time PCR, ELISA, and TUNEL, apoptosis and caspase activation both in vivo and in vitro were significantly increased after severe burn injury, while survivin expression was increased (up to 2.90-fold) during the early stage of burn injury and was almost completely abolished 8 h after the burn. Survivindeficient cardiomyocytes, as well as hearts from rats treated with the survivin inhibitor YM155, exhibited increased caspase-3 protein and mRNA expression and apoptosis ratio at different times after the burn. Furthermore, inhibition of ERK, phosphoinositol 3-kinase contributed the burn serum-induced increase in apoptosis and caspase-3 protein expression, and decreased survivin expression, whereas burn serum-induced increase in apoptosis was attenuated by P38 mitogen-activated protein kinase inhibition. These data identify survivin as a critical anti-apoptotic regulator of cardiomyocytes after burn injury. ERK, P38 MAPK and PI3K were found to be upstream regulators of survivin.
Basic Res Cardio lReceived: 28 March 2011 / Revised: 7 June 2011 / Accepted: 17 June 2011
