Resveratrol protects against hyperglycemia-induced oxidative damage to mitochondria by activating SIRT1 in rat mesangial cells.
Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of diabetic nephropathy (DN). Resveratrol has potent protective effects on diabetes and diabetic complications including diabetic nephropathy. We aimed to investigate the protective effects of resveratrol on mitochondria and the underlying mechanisms by using an in vitro model of hyperglycemia. We exposed primary cultured rat mesangial cells to high glucose (30mM) for 48h. We found that pretreatment with resveratrol (10μM) 6h prior to high glucose treatment significantly reduced hyperglycemia-induced increase in reactive oxygen species (ROS) production and mitochondrial superoxide generation, as well as stimulated MnSOD activity. In addition, resveratrol pretreatment significantly reversed the decrease of mitochondrial complex III activity in glucose-treated mesangial cells, which is considered to be the major source of mitochondrial oxidative stress in glucose-treated cells. Furthermore, resveratrol pretreatment efficiently restored the hyperpolarization of ∆Ψm, increased ATP production and preserved the mtDNA content. All of these protective effects of resveratrol were successfully blocked by siRNA targeting SIRT1 and EX-527, a specific inhibitor of SIRT1 activity. Our results indicated that resveratrol efficiently reduced oxidative stress and maintained mitochondrial function related with activating SIRT1 in glucose-treated mesangial cells. It suggested that resveratrol is pharmacologically promising for treating diabetic nephropathy.
Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, People's Republic of China.
Ying
Y
Xu
Ling
L
Nie
Yang-Guang
YG
Yin
Jian-Lin
JL
Tang
Ji-Yin
JY
Zhou
Dan-Dan
DD
Li
Shi-Wen
SW
Zhou
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy* / Q000503:physiopathology; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D013481:Superoxides; D000255:Adenosine Triphosphate; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D005947:Glucose; D000077185:Resveratrol