Involvement of NAD (P) H Oxidase in a Potential Link between Diabetes and Vascular Smooth Muscle Cell Proliferation.
- Author:
Hye Young JEONG
1
;
Mi Ran YUN
;
Chi Dae KIM
Author Information
1. Department of Pharmacology, College of Medicine, Pusan National University, Busan 602 739, Korea. chidkim@pusan.ac.kr
- Publication Type:Original Article
- Keywords:
Diabetes;
NAD (P) H oxidase;
Superoxide;
VSMC proliferation
- MeSH:
1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt;
Acceleration;
Animals;
Aorta;
Atherosclerosis;
Cell Count;
Cell Proliferation*;
Membranes;
Muscle, Smooth, Vascular*;
NAD*;
Oligonucleotides;
Oxidoreductases*;
Rats;
RNA, Messenger;
Superoxides;
Transfection
- From:The Korean Journal of Physiology and Pharmacology
2003;7(2):103-110
- CountryRepublic of Korea
- Language:English
-
Abstract:
The cellular mechanisms that contribute to the acceleration of atherosclerosis in diabetes are poorly understood. Therefore, the potential mechanisms involved in the diabetes-dependent increase in vascular smooth muscle cell (VSMC) proliferation was investigated. Using primary culture of VSMC from streptozotocin-induced diabetic rat aorta, cell proliferation assay showed two-fold increase in cell number accompanied with enhanced superoxide generation compared to normal VSMC, 2 days after plating. Both the increased superoxide production and cell proliferation in diabetic VSMC were significantly attenuated by not only tiron (1 mM), a superoxide scavenger, but also by diphenyleneiodonium (DPI; 10micrometer), an NAD (P) H oxidase inhibitor. NAD (P) H oxidase activity in diabetic VSMC was significantly higher than that in control cell, accompanied with increased mRNA expression of p22phox, a membrane subunit of oxidase. Furthermore, inhibition of p22phox expression by transfection of antisense p22phox oligonucleotides into diabetic VSMC resulted in a decrease in superoxide production, which was accompanied by a significant inhibition of cell proliferation. Based on these results, it is suggested that diabetes-associated increase in NAD (P) H oxidase activity via enhanced expression of p22phox contributes to augmented VSMC proliferation in diabetic rats.
