Metformin inhibits p38MAPK signaling pathway and oxidativestress in rat glomerular mesangial cells cultured with high glucose

doi:10.12092/j.issn.1009-2501.2018.06.003

Abstract

Abstract:

AIM: To observe relationship between p38MAPK signaling pathway and oxidative stress in rat glomerular mesangial cells (MCs) cultured in high glucose medium and the regulation of metformin. METHODS: Rat glomerular MCs were cultured in a complete medium, and were divided into five groups: normal control group (group NC), high glucose group(group HG) , metformintreated group (group MET), SB203580treated group (group SB), N-acetylcysteinetreated group (group NAC). Intracellular reactive oxygen species (ROS) content of rat glomerular MCs was tested by flow cytometry. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in supernatant fluid were detected by colorimetry and ELISA, respectively. P22phox mRNA of rat glomerular MCs was determined by real-time quantitative PCR. P22phox protein and phosphorylation of p38MAPK(p-p38MAPK)protein of rat glomerular MCs were detected by Western blot. RESULTS: Compared with group NC, the activity of SOD was decreased, whereas the level of MDA, intracellular ROS content, P22phox mRNA and protein, p-p38MAPK protein expression were increased in group HG (P<0.05). When metformin was added to the high glucose medium, the activity of SOD was increased, meanwhile,the level of MDA, intracellular ROS content, P22phox mRNA and protein,pp38MAPK protein expression were decreased (P<0.05), and the results were similar with SB203580 or N-acetylcysteine was added to the high glucose medium (P<0.05). CONCLUSION: Metformin can alleviate high glucose induced oxidative stress and p-p38MAPK protein expression of rat glomerular MCs,which maybe contribute to its renoprotection.

Key words: metformin, oxidative stress, p38 MAPK, mesangial cells

CLC Number:

R965.2

YAO Xinming, KONG Xiang, ZHAO Yongli, HUA Qiang, HE Chunling, YU Dan, LI Yeqiong, DAI Xiaokang, YE Shandong. Metformin inhibits p38MAPK signaling pathway and oxidativestress in rat glomerular mesangial cells cultured with high glucose[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(6): 614-620.

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