A possible target of antioxidative therapy for diabetic vascular complications-vascular NAD(P)H oxidase.
A growing body of evidence has shown that oxidative stress may be involved in the development of vascular complications associated with diabetes. However, the molecular mechanism for increased reactive oxygen species (ROS) production in diabetes remains uncertain. Among various possible mechanisms, attention have increasingly been paid to NAD(P)H oxidase as the most important source of ROS production in vascular cells. High glucose level stimulates ROS production through protein kinase C (PKC)-dependent activation of vascular NAD(P)H oxidase. Furthermore, the expression of NAD(P)H oxidase components is increased in micro- and macrovascular tissues of diabetic animals in association with various functional disorders and histochemical abnormalities. These results suggest that vascular NAD(P)H oxidase-driven ROS production may contribute to the onset or development of diabetic micro- or macrovascular complications. In this point of view, the possible new strategy of antioxidative therapy for diabetic vascular complications is discussed in this review.
Inoguchi
T
T
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. toyoshi@intmed3.med.kyushu-u.ac.jp
Tsubouchi
H
H
Etoh
T
T
Kakimoto
M
M
Sonta
T
T
Utsumi
H
H
Sumimoto
H
H
Yu
H Y
HY
Sonoda
N
N
Inuo
M
M
Sato
N
N
Sekiguchi
N
N
Kobayashi
K
K
Nawata
H
H
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000201:enzymology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D011493:Protein Kinase C; D005947:Glucose