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Pyrroloquinoline quinine protects HK-2 cells against high glucose-induced oxidative stress and apoptosis through Sirt3 and PI3K/Akt/FoxO3a signaling pathway

Author:
Wang, Ziqiang, Li, Ying, Wang, Ying, Zhao, Kunxiao, Chi, Yanqing, Wang, Baoxing
Source:
Biochemical and biophysical research communications 2019 v.508 no.2 pp. 398-404
ISSN:
0006-291X
Subject:
antioxidants, apoptosis, diabetic nephropathy, epithelial cells, gene expression, gene expression regulation, glucose, messenger RNA, models, oxidative stress, pathogenesis, protective effect, proteins, quinine, signal transduction
Abstract:
High glucose(HG)-induced oxidative stress and apoptosis in renal tubular epithelial cells play an important role in the pathogenesis of diabetic nephropathy. Pyrroloquinoline quinine (PQQ), a new B vitamin, has been demonstrated to be important in antioxidant and anti-apoptotic effects. However, its effect on HK-2 cells and the potential mechanism are rarely investigated. In this study, we investigated that PPQ had protective effects against HG-induced oxidative stress damage and apoptosis in vitro model of diabetic nephropathy. PPQ at 10, 100, 500, 1000 and 10000 nM could protect HK-2 cell from HG-induced inhibition. The protective effects of PQQ were associated with increasing the level of antioxidants(SOD2, CAT), inhibition of reactive oxygen species(ROS) production, and dependent modulation of Bcl-2 family proteins. PPQ significantly upregulated the protein and mRNA expression of Sirtuin3(Sirt3) in HG-induced HK-2 cells. PPQ also reduced apoptosis in HG-induced HK-2 cells by the PI3K/Akt/FoxO3a signal pathway. As down-regulated sirt3 or inhibitory the activity of PI3K/Akt/FoxO3a pathway, the protective effects of PPQ were weakened. In conclusion, our data suggest that PPQ achieves the protective effects through PI3K/Akt/FoxO3a pathway and dependent modulation of Sirt3.
Agid:
6225577