Enhanced vascular production of superoxide in OLETF rat after the onset of hyperglycemia.
This study was aimed to characterize the vascular production of superoxide in Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type 2 diabetes. The nitroblue tetrazolium staining in the aorta from old (30 weeks) OLETF rat was more prominent than that of age-matched control (LETO) rat, which was significantly inhibited by diphenyleneiodonium (10 micromol/l), but not by inhibitors for other oxidases such as xanthine oxidase, mitochondrial oxidase, nitric oxide synthase, and cyclooxygenase. In the aorta from old OLETF rat with hyperglycemia, the enhanced NADH oxidase activity in association with upregulated expression of p22phox and gp91phox was observed, but not in both LETO and young (10 weeks) OLETF rats without hyperglycemia. Furthermore, there was a positive correlation (P<0.01) between elevation of blood glucose level and increase in vascular NADH oxidase activity. Based on these results, it was suggested that the enhanced NADH oxidase activity in the aorta from OLETF rat occurred after the onset of hyperglycemia, thereby resulting in the increased vascular production of superoxide.
Kim
In J
IJ
Department of Internal Medicine and Pharmacology, College of Medicine, Pusan National University, Busan 602-739, South Korea.
Kim
Yong K
YK
Son
Seok M
SM
Hong
Ki W
KW
Kim
Chi D
CD
D000375:Aging; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D012016:Reference Values; D013481:Superoxides / Q000378:metabolism*
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes; D010750:Phosphoproteins; D013481:Superoxides; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase