title: Impaired mitochondrial complex III and melatonin responsive reactive oxygen species generation in kidney mitochondria of db/db mice.
abstract: We have previously demonstrated that melatonin, at pharmacological concentrations, causes rapid reactive oxygen species (ROS) generation at the antimycin-A sensitive site of mitochondrial complex III (MC-3). In the current work, we used this melatonin response to investigate the role of mitochondrial dysfunction in the development of diabetic nephropathy. We find that the development of diabetic nephropathy, as indicated by hyperfiltration and histopathological lesions in the kidney of db/db mice, is associated with diminished melatonin-induced ROS generation and MC-3 activity, indicating impaired MC-3 at the antimycin-A site. The MC-3 protein level in the renal mitochondria was equivalent in db/db and the nondiabetic db/m mice, whereas mitochondrial complex I (MC-1) protein was dramatically upregulated in the db/db mice. This differential regulation in mitochondrial complexes may alter the equilibrium of the electron transport in renal mitochondria and contribute to ROS overproduction. The study provides one mechanism of enhanced oxidative stress that may be involved in the pathogenesis of diabetic nephropathy in db/db mice.
authors: Department of Geriatrics, Xijing Hospital, Xi'An, China.
authors: Hua
authors: H
authors: Zhang
authors: Hong-Mei
authors: HM
authors: Zhang
authors: Li-Ping
authors: LP
authors: Wu
authors: Dun-Xian
authors: DX
authors: Tan
authors: Amrita
authors: A
authors: Kamat
authors: Yun-Qing
authors: YQ
authors: Li
authors: Michael S
authors: MS
authors: Katz
authors: Hanna E
authors: HE
authors: Abboud
authors: Russel J
authors: RJ
authors: Reiter
authors: Bin-Xian
authors: BX
authors: Zhang
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