Adiponectin inhibits the generation of reactive oxygen species induced by high glucose and promotes endothelial NO synthase formation in human mesangial cells

Yuan,Fang; Li,Yi-Ning; Liu,Ying-Hong; Yi,Bin; Tian,Jun-Wei; Liu,Fu-You

doi:10.3892/mmr.2012.931

Adiponectin inhibits the generation of reactive oxygen species induced by high glucose and promotes endothelial NO synthase formation in human mesangial cells

Authors:
- Fang Yuan
- Yi-Ning Li
- Ying-Hong Liu
- Bin Yi
- Jun-Wei Tian
- Fu-You Liu
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Affiliations: Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
Published online on: May 29, 2012 https://doi.org/10.3892/mmr.2012.931
Pages: 449-453

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Abstract

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.

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1	Stojiljkovic L and Behnia R: Role of renin angiotensin system inhibitors in cardiovascular and renal protection: a lesson from clinical trials. Curr Pharm Des. 13:1335–1345. 2007. View Article : Google Scholar : PubMed/NCBI
2	Suzuki S, Hinokio Y, Komatu K, et al: Oxidative damage to mitochondrial DNA and its relationship to diabetic nephropathy. Diabetes Res Clin Pract. 45:161–168. 1999. View Article : Google Scholar : PubMed/NCBI
3	Okamoto Y, Kihara S, Ouchi N, et al: Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 106:2767–2770. 2002. View Article : Google Scholar : PubMed/NCBI
4	Yilmaz MI, Saglam M, Qureshi AR, et al: Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin. Nephrol Dail Transplant. 23:1621–1627. 2008. View Article : Google Scholar : PubMed/NCBI
5	Saraheimo M, Forsblom C and Fagerudd J: Serum adiponectin is increased in type 1 diabetic patients with nephropathy. Diabetes Care. 28:1410–1414. 2005. View Article : Google Scholar : PubMed/NCBI
6	Schalkwijk CG, Chaturvedi N, Schram MT, et al: Adiponectin is inversely associated with renal function in type 1 diabetic patients. J Clin Endocrinol Metab. 91:129–135. 2006. View Article : Google Scholar : PubMed/NCBI
7	Fujita H, Morii T, Koshimura J, et al: Possible relationship between adiponectin and renal tubular injury in diabetic nephropathy. Endocr J. 53:745–752. 2006. View Article : Google Scholar : PubMed/NCBI
8	Nishikawa T, Edelstein D and Du XL: Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature. 404:787–790. 2000. View Article : Google Scholar : PubMed/NCBI
9	Stokes KY, Clanton EC, Russell JM, et al: NAD (P) H oxidase-derived superoxide mediates hypercholesterolemia-induced leukocyte-endothelial cell adhesion. Circ Res. 88:499–505. 2001. View Article : Google Scholar : PubMed/NCBI
10	Rueckschloss U, Galle J, Holtz J, et al: Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of hydroxyme thylglutaryl coenzyme A reductase inhibitor therapy. Circulation. 104:1767–1772. 2001. View Article : Google Scholar
11	Xu Y, Osborne BW and Stanton RC: Diabetes causes inhibition of glucose-6-phosphate dehydrogenase via activation of PKA, which contributes to oxidative stress in rat kidney cortex. Am J Physiol Renal Physiol. 289:1040–1047. 2005. View Article : Google Scholar : PubMed/NCBI
12	Ha H, Yang Y, Lee HB, et al: Mechanisms of reactive oxygen species generetion in LLC2PK1 cells cultured under high glucose. J Am Soc Nephrol. 13:531A2002.
13	Davila-Esqueda ME, Vertiz-Hernandez AA and Martinez-Morales F: Comparative analysis of the renoprotective effects of pentoxifylline and vitamin E on streptozotocin-induced diabetes mellitus. Ren Fail. 27:115–122. 2005.PubMed/NCBI
14	Chen L, Jia RH, Ding GH, et al: Effect of irbesartan on oxidative stress and the activity of protein kinase C in type 2 diabetic rats. Wu Han Da Xue Xue Bao (Yi Xue Ban). 25:150–153. 2004.
15	Motoshima H, Wu X, Mahadev K, et al: Adiponectin suppresses proliferation an superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. Biochem Biophys Res Commun. 315:264–271. 2004. View Article : Google Scholar : PubMed/NCBI
16	Ge Q, Deng HC and Liu JB: Effect of adiponectin on endothelial function. Chin J Endocrinol Metab. 1:15–18. 2006.
17	Pritchard KA Jr, Groszek L, Smalley DM, et al: Native low-density lipoprotein increases endothelial cell nitric oxide synthase generation of superoxide anion. Circ Res. 77:510–518. 1995. View Article : Google Scholar : PubMed/NCBI
18	Ha H and Lee HB: Reactive oxygen species amplify glucose signalling in renal cells cultured under high glucose and in diabetic kidney. Nephrology. 1:7–10. 2005. View Article : Google Scholar : PubMed/NCBI
19	Yamauchi T, Kamon J, Ito Y, et al: Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 423:762–769. 2003. View Article : Google Scholar : PubMed/NCBI
20	Chen H, Montagnani M, Funahashi T, et al: Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem. 278:45021–45026. 2003. View Article : Google Scholar : PubMed/NCBI