Involvement of NAD(P)H oxidase in the enhanced expression of cell adhesion molecules in the aorta of diabetic mice.
The increased levels of cell adhesion molecules (CAM) have been identified in diabetic vasculatures, but the underlying mechanisms remain unclear. To determine the relationship among vascular production of superoxide, expression of CAM and diabetes, superoxide generation and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E- and P-selectin in the aorta from control (C57BL/6J) and diabetic mice (ob/ob) were measured. In situ staining for superoxide using dihydroethidium showed an increased superoxide production in diabetic aorta in association with an enhanced NAD(P)H oxidase activity. Immunohistochemical analysis revealed that the endothelial expression of ICAM-1 (3.5 +/- 0.4) and VCAM-1 (3.8 +/- 0.3) in diabetic aorta was significantly higher than that in control aorta (0.9 +/- 0.5 and 1.6 +/- 0.3, respectively). Furthermore, there was a strong positive correlation (r = 0.89, p < 0.01 in ICAM-1 and r = 0.88, p < 0.01 in VCAM-1) between ICAM-1/VCAM-1 expression and vascular production of superoxide. The present data indicate that the increased production of superoxide via NAD(P)H oxidase may explain the enhanced expression of CAM in diabetic vasculatures.
Yun
Mi Ran
MR
Department of Pharmacology, College of Medicine and Pharmacy, Research Institute of Genetic Engineering, Pusan National University, 10 Ami-Dong 1-Ga, Seo-Gu, Busan 602-739, South Korea.
Kim
Jong Jae
JJ
Im
Dong Sun
DS
Yang
Seung Don
SD
Kim
Chi Dae
CD
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002448:Cell Adhesion; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D004996:Ethidium / Q000031:analogs & derivatives* / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D019255:NADPH Oxidases; D019007:P-Selectin / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D019040:E-Selectin; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; C067883:dihydroethidium; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D004996:Ethidium