Adiponectin inhibits the generation of reactive oxygen species induced             by high glucose and promotes endothelial NO synthase formation in human mesangial             cells.
The aim of this study was to investigate the effects of adiponectin (ADPN) on high glucose (HG)-induced reactive oxygen species (ROS) and the formation of endothelial nitric oxide (NO) synthase (eNOS) in human glomerular mesangial cells (HMCs), as well as to determine which signaling pathways are modulated by ADPN and the mechanisms involved. HMCs cultured in vitro were randomly divided into 4 groups: the control, HG, HG + globular adiponectin (gAd) and HG + gAd + adenine arabinoside (AraA). The generation of ROS was detected using a fluorescent probe. The mRNA expression and protein levels of eNOS were measured by RT-PCR and western blot analysis, respectively. The phosphorylation of AMP-activated protein kinase (AMPK) was assessed by western blot analysis. HMCs treated with ADPN revealed the time-dependent phosphorylation of AMPK. The treatment of HMCs with HG resulted in increased release of ROS and decreased expression of eNOS compared to the control group (p<0.05). Cells treated with ADPN showed a decrease in HG-induced ROS (p<0.05) and an upregulated eNOS expression. The effects of gAd were partly blocked by the AMPK inhibitor, AraA. The results from the present study show that ADPN inhibits the generation of HG-induced ROS in HMCs; it also stimulates eNOS activity, which has a protective effect. The mechanism partly occurs through the stimulation of the AMPK signaling pathway.
Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Fang
F
Yuan
Yi-Ning
YN
Li
Ying-Hong
YH
Liu
Bin
B
Yi
Jun-Wei
JW
Tian
Fu-You
FY
Liu
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors; D052242:Adiponectin / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D050527:Mesangial Cells / Q000187:drug effects* / Q000201:enzymology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014740:Vidarabine / Q000494:pharmacology
D052242:Adiponectin; D003470:Culture Media; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D055372:AMP-Activated Protein Kinases; D014740:Vidarabine; D005947:Glucose