title: Calcineurin mediates the protective effect of postconditioning on skeletal muscle.
abstract: We aimed to investigate whether ischemic postconditioning (I-postC) protects skeletal muscle against ischemia-reperfusion (I/R) injury through the calcineurin (CaN) pathway. Male Wistar rats underwent 4 h of right-hind-limb ischemia induced by clamping the femoral artery, then reperfusion for 2 h (I/R-2 h), 12 h (I/R-12 h), or 24 h (I/R-24 h) with or without I-postC. Ischemic postconditioning was induced by three cycles of 1-min reperfusion and 1-min ischemia at the onset of reperfusion after prolonged ischemia. The I-postC-24 h group was treated with or without cyclosporine A (a CaN inhibitor) 10 mg/kg per day for 3 days before artery occlusion. Cultured skeletal muscle cells (SMCs) from neonatal rats were exposed to 2-h hypoxia then 24-h reoxygenation (H/R), then postconditioned with two cycles of 10-min reoxygenation and 10-min hypoxia after prolonged hypoxia (hypoxia postconditioning [H-postC]) in the presence or absence of cyclosporine A. We observed the effects of activated CaN overexpression on apoptosis and viability of SMCs under H-postC. Ischemic postconditioning attenuated the increase in the level of malondialdehyde in skeletal muscle induced by I/R-2 h and I/R-24 h (P < 0.05) and lactate dehydrogenase in plasma induced by I/R-12 h and I/R-24 h (P < 0.05). Cyclosporine A abolished the protective role of I-postC in malondialdehyde level and lactate dehydrogenase leakage (P < 0.05, vs. I-postC group). Hypoxia postconditioning suppressed SMC apoptosis induced by H/R (P < 0.05, vs. H/R), which was accompanied by increased CaN expression. Cyclosporine A abolished the antiapoptotic effect of H-postC on SMCs (P < 0.05, vs. H-postC group). Overexpression of activated CaN strengthened the cytoprotection of H-postC (P < 0.05, vs. H-postC group). Ischemic postconditioning may protect skeletal muscle against I/R injury through the CaN pathway.
authors: Department of Pathophysiology, Medicine School of Shandong University, Jinan, China.
authors: Xiao-Sun
authors: XS
authors: Guo
authors: Yu-Zhen
authors: YZ
authors: Li
authors: Xiu-Hua
authors: XH
authors: Liu
authors: Zhen-Ying
authors: ZY
authors: Zhang
authors: Feng-Ying
authors: FY
authors: Liu
authors: Wei-Cheng
authors: WC
authors: Hu