Abstract | BACKGROUND: METHOD: Molecular and structural changes involved in the pathogenesis of DN were tested in a rat model of early-stage diabetes. Renal mesangial cells (RMCs) were cultured in media containing different concentrations of glucose with or without resveratrol. Cellular DNA synthesis was assayed by measuring (3)H-thymidine incorporation. The phosphorylation status of AMPK, eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), and phospho- ribosomal protein S6 (S6) was analyzed by Western blot. RESULTS:
Resveratrol reduced plasma creatinine and urinary albumin excretion and attenuated renal hypertrophy without affecting blood glucose levels. Moreover, resveratrol activated AMPK and inhibited phosphorylation of 4E-BP1 and S6 in diabetic rat kidneys. In vitro, resveratrol blocked high glucose-induced dephosphorylation of AMPK and phosphorylation of 4E-BP1 and S6 and strongly inhibited both the DNA synthesis and proliferation of RMCs. CONCLUSION: These findings suggest the possibility that resveratrol exerts antiproliferative, antihypertrophic effects by activating AMPK and reducing 4E-BP1 and S6 phosphorylation, thus suppressing the development and progression of DN.
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Authors | Da-Fa Ding, Na You, Xiao-Mei Wu, Jia-Rong Xu, Ai-Ping Hu, Xiao-Long Ye, Qun Zhu, Xiu-Qing Jiang, Heng Miao, Chao Liu, Yi-Bing Lu |
Journal | American journal of nephrology
(Am J Nephrol)
Vol. 31
Issue 4
Pg. 363-74
( 2010)
ISSN: 1421-9670 [Electronic] Switzerland |
PMID | 20332614
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | 2010 S. Karger AG, Basel. |
Chemical References |
- Stilbenes
- Protein Kinases
- AMP-Activated Protein Kinase Kinases
- Resveratrol
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Topics |
- AMP-Activated Protein Kinase Kinases
- Animals
- Diabetic Nephropathies
(prevention & control)
- Hypertrophy
(prevention & control)
- Kidney
(pathology)
- Male
- Phosphorylation
(drug effects)
- Protein Kinases
(metabolism, physiology)
- Rats
- Rats, Sprague-Dawley
- Resveratrol
- Stilbenes
(pharmacology, therapeutic use)
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