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

Chemico-biological Interactions
Junghyun KimJin Sook Kim

Abstract

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 400muM MGO for 6h. Retinal vessels were prepared from intravitreally MGO-injected rat eyes. We demonstrated apoptosis, nuclear factor-kappaB (NF-kappaB) 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-kappaB was translocalized into the nuclei of pericytes, which paralleled the expression of iNOS. The treatment of pyrrolidine dithiocarbamate (an NF-kappaB inhibitor) or l-N6-(1-iminoethyl)-lysine (an iNOS inhibitor) prevented apoptosis of MGO-treated pericytes. In addition, in intravitreally MGO-injected rat eyes, T...Continue Reading

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Citations

Jan 18, 2012·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Junghyun KimJin Sook Kim
Sep 18, 2012·Endocrine·Paulo MatafomeRaquel Seiça
Dec 18, 2013·International Journal of Environmental Research and Public Health·Woody R McGinnisStephen M Edelson
Feb 24, 2016·Free Radical Biology & Medicine·James M May
Aug 26, 2014·Biochemical and Biophysical Research Communications·James M MayWilliam H Parker
Sep 17, 2016·Medicinal Research Reviews·Paulo MatafomeRaquel Seiça
Feb 5, 2013·Metabolic Brain Disease·Luana HeimfarthRegina Pessoa-Pureur
Jul 25, 2019·Cells·Cecilia NigroClaudia Miele

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