Cytotoxic role of methylglyoxal in rat retinal pericytes: Involvement of a nuclear factor-kappaB and inducible nitric oxide synthase pathway

被引:27
作者
Kim, Junghyun [1 ]
Kim, Ohn Soon [1 ]
Kim, Chan-Sik [1 ]
Kim, Nan Hee [1 ]
Kim, Jin Sook [1 ]
机构
[1] Korea Inst Oriental Med, Div Tradit Korean Med TKM Integrated Res, Diabet Complicat Res Ctr, Taejon 305811, South Korea
关键词
Apoptosis; Inducible nitric oxide synthase; Methylglyoxal; Nuclear factor-kappaB; Rat retinal pericytes; GLYCATION END-PRODUCTS; DIABETIC-RETINOPATHY; ENDOTHELIAL-CELLS; B ACTIVATION; PYRROLIDINE DITHIOCARBAMATE; INDUCED APOPTOSIS; OXIDATIVE STRESS; MESANGIAL CELLS; MUSCLE-CELLS; SERUM-LEVELS;
D O I
10.1016/j.cbi.2010.07.002
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
Methylglyoxal (MGO), a cytotoxic metabolite, is produced from glycolysis. Elevated levels of MGO are observed in a number of diabetic complications, including retinopathy, nephropathy and cardiomyopathy. Loss of retinal pericyte, a hallmark of early diabetic retinal changes, leads to the development of formation of microaneurysms, retinal hemorrhages and neovasculization. Herein, we evaluated the cytotoxic role of MGO in retinal pericytes and further investigated the signaling pathway leading to cell death. Rat primary retinal pericytes were exposed to 400 mu M MGO for 6 h. Retinal vessels were prepared from intravitreally MGO-injected rat eyes. We demonstrated apoptosis, nuclear factor-kappaB (NF-kappa B) activation and inducible nitric oxide synthase (iNOS) induction in cultured pericytes treated with MGO and MGO-injected retinal vessels. In MGO-treated pericytes, TUNEL-positive nuclei were markedly increased, and NF-kappa B was translocalized into the nuclei of pericytes, which paralleled the expression of iNOS. The treatment of pyrrolidine dithiocarbamate (an NF-kappa B inhibitor) or L-N6-(1-iminoethyl)-lysine (an iNOS inhibitor) prevented apoptosis of MGO-treated pericytes. In addition, in intravitreally MGO-injected rat eyes, TUNEL and caspase-3-positive pericytes were significantly increased, and activated NF-kappa B and iNOS were highly expressed. These results suggest that the increased expression of NF-kappa B and iNOS caused by MGO is involved in rat retinal pericyte apoptosis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:86 / 93
页数:8
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