The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Involvement of NAD(P)H Oxidase in a Potential Link between Diabetes and Vascular Smooth Muscle Cell Proliferation

  • Jeong, Hye-Young (Department of Pharmacology, College of Medicine, Pusan National University) ;
  • Yun, Mi-Ran (Department of Pharmacology, College of Medicine, Pusan National University) ;
  • Kim, Chi-Dae (Department of Pharmacology, College of Medicine, Pusan National University)
  • Published : 2003.04.21
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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; $10{\mu}M$), 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.

Keywords

References

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