Cytoprotection against hydrogen peroxide-induced cell death in cultured mouse mesangial cells by erigeroflavanone, a novel compound from the flowers of Erigeron annuus

被引:11
作者
Kim, Ohn Soon [1 ]
Kim, Young Sook [1 ]
Jang, Dae Sik [1 ]
Yoo, Nam Hee [1 ]
Kim, Jin Sook [1 ]
机构
[1] Korea Inst Oriental Med, Diabet Complicat Res Ctr, Div Tradit Korean Med TKM Integrated Res, Taejon 305811, South Korea
关键词
Erigeroflavanone; Mesangial cells; Cell death; Diabetic nephropathy; Antioxidant effect; MAPKs; Caspase-3; STRESS-INDUCED APOPTOSIS; OXIDATIVE STRESS; DIABETIC-NEPHROPATHY; ADVANCED GLYCATION; SIGNALING PATHWAY; PROTEIN GLYCATION; GLUCOSE; COMPLICATIONS; PATHOBIOLOGY; ALBUMINURIA;
D O I
10.1016/j.cbi.2009.03.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hyperglycemia-induced oxidative stress has been suggested as a mechanism underlying diabetic complications. Oxidative stress triggers cell death in various cell types, including glomerular mesangial cells which play important roles in diabetic nephropathy. In the present study, we investigated the potential cytoprotective effect of erigeroflavanone, a novel flavanone derivative from the flowers of Erigeron annuus, in cultured mouse mesangial cells using hydrogen peroxide (H2O2) as an oxidative stress inducer. Our data show that hydrogen peroxide induced a decrease in cell viability that was attenuated by erigeroflavanone. Hydrogen peroxide treatment increased formation of dichlorofluorescein (DCF)-sensitive intracellular reactive oxygen species (ROS). This enhanced ROS formation was significantly reduced by pretreatment with erigeroflavanone in a dose-dependent manner. Hydrogen peroxide treatment also induced phosphorylation of the mitogen-activated protein kinases (MAPKs), c-Jun terminal kinase (JNK), extracellular-regulated kinase (ERK) and p38, and activated caspase-3. Pretreatment with erigeroflavanone inhibited hydrogen peroxide-induced activation of MAPKs and caspase-3. From these data we conclude that erigeroflavanone provides a protective effect against oxidative stress-induced cell death in mesangial cells that is associated with its antioxidant action and inhibition of MAPKs and caspase-3. These results suggest that erigeroflavanone has potential as a therapeutic agent in the treatment of renal diabetic complications. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:414 / 420
页数:7
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