Renal podocyte apoptosis in Zucker diabetic fatty rats: involvement of methylglyoxal-induced oxidative DNA damage.
Methylglyoxal (MGO) is a cytotoxic metabolite produced by in-vivo glycolysis that may result in diabetic complications. The aim of this study was to determine whether MGO and oxidative stress caused apoptosis of renal podocytes in the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes mellitus. Male ZDF rats aged 21 weeks developed marked hyperglycaemia with proteinuria and albuminuria. Immunohistochemical evaluation of sections of kidney demonstrated expression of MGO and 8-hydroxydeoxyguanosine (8-OHdG) in the podocytes of both normoglycaemic and diabetic rats. Podocyte apoptosis was shown through application of the TUNEL method. These findings suggest that expression of MGO and 8-OHdG is caused by hyperglycaemia, and that this expression is associated with the observed apoptosis of podocytes and is related to diabetic nephropathy.
Kim
J
J
Diabetic Complications Research Center, Division of Traditional Korean Medicine (TKM) Integrated Research, Korea Institute of Oriental Medicine, Daejeon, South Korea. jskim@kiom.re.kr
Sohn
E
E
Kim
C-S
CS
Kim
J S
JS
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D011765:Pyruvaldehyde / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker
D011765:Pyruvaldehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine