title: Ursolic acid prevents endoplasmic reticulum stress-mediated apoptosis induced by heat stress in mouse cardiac myocytes.
abstract: Heat stress causes serious physiological dysfunction of cardiac myocytes and is associated with several types of cardiovascular diseases. However, the underlying mechanisms and therapeutic strategies to alleviate heat stress-induced myocardial damage are not available. The objective of this study was to (1) investigate the functional role of endoplasmic reticulum (ER) stress-mediated apoptosis in heat exposure-induced myocardial damage, and (2) to evaluate the effects of ursolic acid on the myocardial apoptosis as well as the underlying mechanisms in mouse cardiac myocytes. We show here that heat stress-induced apoptosis is predominantly mediated by the activation of PERK-eIF2α-CHOP unfolded protein response which up-regulates the protein expression of Puma, and by the modulation of cellular redox state. Intriguingly, the myocardial apoptosis is markedly attenuated by ursolic acid treatment. Mechanistically, the protective effects of ursolic acid are mediated, at least partly, by reestablishing the intracellular redox state and inducing the expression of the anti-apoptotic protein Mcl-1, which, in turn, inactivating CHOP-induced Puma up-regulation. The striking finding that ursolic acid has both anti-apoptotic and antioxidative activities against ER stress-associated myocardial damage suggests that supplementation of ursolic acid might be a potential strategy to reduce the detrimental effects of heat stress in cardiomyocytes.
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China.
authors.forename: Changwu
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China.
authors.forename: Zhaolai
authors.initials: Z
authors.lastname: Dai
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, PR China.
authors.forename: Meijia
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China. Electronic address: guoym9899@yahoo.com.cn.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, PR China. Electronic address: bio2046@hotmail.com.
authors.forename: Zhenlong
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects*; D018869:Heat-Shock Response; D006358:Hot Temperature; D051379:Mice; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D016861:Cyclooxygenase Inhibitors; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: Apoptosis; Cardiac myocytes; Heat stress; Ursolic acid