Toll-like receptor 7/8 agonist resiquimod induces late preconditioning in neonatal cardiac myocytes  

作　　者：Yong-yi WANG Sha LIU Feng LIAN Wen-gang YANG Song XUE 

机构地区：[1]Department of Cardiovascular Surgery, RenJi Hospital of Shanghai Jiaotong University, Shanghai 200127, China

出　　处：《Acta Pharmacologica Sinica》2011年第5期565-572,共8页中国药理学报（英文版）

摘　　要：Aim： To investigate whether R-848 （resiquimod, toll-like receptor 7/8 agonist） can induce late preconditioning in neonatal cardiac myocytes. Methods： The protective effects of R-848 on neonatal myocytes against anoxia-reoxygenation-induced injury were tested, and intracellular reactive oxygen species （ROS） were determined. The protein synthesis inhibitor cyclohexamide （CH） and the ROS scavenger N-acetylcysteine （NAC） were used in this model to test if new protein synthesis and oxidative stress were necessary for their cardioprotective effects. The activation of nuclear factor kappa B （NFKB） and hypoxia inducible factor 1 （HIF1） was investigated by electrophoretic mobility shift assays （EMSA）, and inducible nitric oxide synthase （iNOS） was assessed by immunoblotting. After iNOS was downregulated by small interfering RNA （siRNA） transfection, the cardioprotective effect was reassessed. Results： ROS were triggered soon after R-848 （0.01-1.0 pg/L） administration, however, the cardioprotective effect of which was induced 24 h later. This protection was abolished by CH or NAC pretreatment. NFKB and HIF1 activation and iNOS up-regulation were involved in this protective mechanism. The cardioprotective effect was also attenuated after iNOS was knocked down. Conclusion： R-848 provided a cardioprotective effect through a late preconditioning mechanism via a ROS/NFKB-HIF1/iNOS-dependent pathway.Aim： To investigate whether R-848 （resiquimod, toll-like receptor 7/8 agonist） can induce late preconditioning in neonatal cardiac myocytes. Methods： The protective effects of R-848 on neonatal myocytes against anoxia-reoxygenation-induced injury were tested, and intracellular reactive oxygen species （ROS） were determined. The protein synthesis inhibitor cyclohexamide （CH） and the ROS scavenger N-acetylcysteine （NAC） were used in this model to test if new protein synthesis and oxidative stress were necessary for their cardioprotective effects. The activation of nuclear factor kappa B （NFKB） and hypoxia inducible factor 1 （HIF1） was investigated by electrophoretic mobility shift assays （EMSA）, and inducible nitric oxide synthase （iNOS） was assessed by immunoblotting. After iNOS was downregulated by small interfering RNA （siRNA） transfection, the cardioprotective effect was reassessed. Results： ROS were triggered soon after R-848 （0.01-1.0 pg/L） administration, however, the cardioprotective effect of which was induced 24 h later. This protection was abolished by CH or NAC pretreatment. NFKB and HIF1 activation and iNOS up-regulation were involved in this protective mechanism. The cardioprotective effect was also attenuated after iNOS was knocked down. Conclusion： R-848 provided a cardioprotective effect through a late preconditioning mechanism via a ROS/NFKB-HIF1/iNOS-dependent pathway.

关 键 词：toll like receptor RESIQUIMOD late preconditioning anoxia-reoxygenation reactive oxygen species CARDIOPROTECTION 

分 类 号：Q257[生物学—细胞生物学] S852.3[农业科学—基础兽医学]