title: Insulin-mediated inhibition of p38 mitogen-activated protein kinase protects cardiomyocytes in severe burns.
abstract: Thermal injury inhibits Akt activation and upregulates p38 mitogen-activated protein kinase, which in turn induces inflammation and increases apoptosis. This study aimed to elucidate the mechanism underlying the cytoprotective role of insulin in severe burns by examining the effects of insulin on inflammation and apoptosis mediated by p38 mitogen-activated protein kinase in burn serum-challenged cardiomyocytes. Neonatal rat cardiomyocytes were exposed to burn serum for 6 hours in the presence or absence of insulin and pretreated with inhibitors to p38 mitogen-activated protein kinase (SB203580) and Akt (LY294002). The authors examined expression of myocardial tumor necrosis factor-alpha, cardiac myofilament proteins caspase-3 and Bcl2, and apoptosis. Burn serum-induced upregulation of tumor necrosis factor was inhibited by both SB203580 and insulin. LY294002 reversed insulin-mediated downregulation of tumor necrosis factor. Both SB203580 and insulin inhibited apoptosis, resulting in fewer pyknotic nuclei and inhibition of caspase-3 activation and Bcl2 downregulation. LY294002 reversed insulin-mediated inhibition of apoptosis. Insulin decreases inflammatory cytokine expression and apoptosis via PI3K/Akt-mediated inhibition of p38 mitogen-activated protein kinase. The cytoprotective role of insulin suggests that it may have a potential role in strategies for treating thermal injuries.
authors.affiliation: Burn Centre, Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Gen-fa
authors.initials: GF
authors.lastname: Lv
authors.forename: Mao-long
authors.initials: ML
authors.lastname: Dong
authors.forename: Da-hai
authors.initials: DH
authors.lastname: Hu
authors.forename: Wan-fu
authors.initials: WF
authors.lastname: Zhang
authors.forename: Yun-chuan
authors.initials: YC
authors.lastname: Wang
authors.forename: Chao-wu
authors.initials: CW
authors.lastname: Tang
authors.forename: Xiong-xiang
authors.initials: XX
authors.lastname: Zhu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D002056:Burns / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis; D061945:Caspase Inhibitors; D004195:Disease Models, Animal; D015870:Gene Expression; D007249:Inflammation / Q000517:prevention & control; D007328:Insulin / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D061945:Caspase Inhibitors; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3