Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes: role of vascular NAD(P)H oxidase.
Hyperglycemia seems to be an important causative factor in the development of micro- and macrovascular complications in patients with diabetes. Several hypotheses have been proposed to explain the adverse effects of hyperglycemia on vascular cells. Both protein kinase C (PKC) activation and oxidative stress theories have increasingly received attention in recent years. This article shows a PKC-dependent increase in oxidative stress in diabetic vascular tissues. High glucose level stimulated reactive oxygen species (ROS) production via a PKC-dependent activation of NAD(P)H oxidase in cultured aortic endothelial cells, smooth muscle cells, and renal mesangial cells. In addition, expression of NAD(P)H oxidase components were shown to be upregulated in vascular tissues and kidney from animal models of diabetes. Furthermore, several agents that were expected to block the mechanism of a PKC-dependent activation of NAD(P)H oxidase clearly inhibited the increased oxidative stress in diabetic animals, as assessed by in vivo electron spin resonance method. Taken together, these findings strongly suggest that the PKC-dependent activation of NAD(P)H oxidase may be an essential mechanism responsible for increased oxidative stress in diabetes.
Inoguchi
Toyoshi
T
Departments of Medicine and Bioregulatory Science and Molecular and Structure Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. toyoshi@intmed3.med.jyushu-u.ac.jp
Sonta
Toshiyo
T
Tsubouchi
Hirotaka
H
Etoh
Takashi
T
Kakimoto
Maiko
M
Sonoda
Noriyuki
N
Sato
Naoichi
N
Sekiguchi
Naotaka
N
Kobayashi
Kunihisa
K
Sumimoto
Hideki
H
Utsumi
Hideo
H
Nawata
Hajime
H
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism*; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D011493:Protein Kinase C