(The FASEB Journal. 2007;21:732.11)
© 2007 FASEB
Methylglyoxal induces oxidative stress in aortic endothelial cells.
Noriko Miyazawa1,
Michiaki Abe1,
Hiroyuki Terawaki2,
Keisuke Nakayama2,
Takafumi Toyohara1,
Eisuke Shibata1,
Masayuki Tanemoto1,
Takaaki Abe1,
Masaaki Nakayama2 and
Sadayoshi Ito1
1 Kidney, endocrinology and vascular medicine, Tohoku university, 1-1, seiryocho, aoba-ku, Sendai, 980-8574, Japan,
2 Research division of dialysis and chronic kidney disease, Tohoku university, 1-1, seiryocho, aoba-ku, Sendai city, 980-8574, Japan
ABSTRACT
The diabetic vascular complications are associated with cell injury due to oxidative stress. Methylglyoxal (MGO), a carbonyl compound derived non-enzymatically from glucose through fluctose, has been known to induce oxidative stress. MGO is a high reactive molecule and previous studies showed that MGO regulated MAPK, changed cell signaling and induced apoptosis. However, as MGO does not produce superoxide chemically by itself, and the mechanism of induction of oxidative stress remains to be clarified. We examined how MGO produces oxidative stress biologically. Human endothelial cells cultured attached on cover slips were assessed under a real-time fluorescent microscopy with a continuous-superfusion system. Intracellular level of oxidative stress was evaluated by the increasing intensity of DCF-DA. Addition of MGO significantly stimulated intracellular oxidative stress in a dose-dependent manner. The responses were inhibited by a superoxide scavenger. Pretreatment with PEG-Catalase, a mitochondrial uncouplar, or a mitochondrial complex inhibitor completely inhibited the MGO-induced oxidative stress. Pretreatment with 1mM apocynin, an NADPH oxidase inhibitor inhibited partially. These data suggested that MGO stimulated superoxide anion primarily mitochondrial pathway, which may be linked to cytosolic NADPH pathway in endothelial cells.
