Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resveratrol.
Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5 μMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein expression in FLSs. But, resveratrol could reverse these effects by changing mitochondrial membrane potential (Δψm) to promote mitochondrial reactive oxygen species (mtROS) generation in 5 μMH2O2-treatment FLSs. These results suggest that oxidative stress existed in AA rats. Resveratrol could suppress oxidative stress in AA rats and increase mtROS production by reducing autophagy protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of resveratrol confers patients with rheumatoid arthritis.
Department of Histology and Embryology, Anhui Medical University, Hefei 230032, China.
Junqiang
J
Zhang
Basic Medicine, Anhui Medical College, Hefei 230601, China.
Xianbin
X
Song
Department of Histology and Embryology, Anhui Medical University, Hefei 230032, China.
Wei
W
Cao
Department of Histology and Embryology, Anhui Medical University, Hefei 230032, China.
Jinseng
J
Lu
Basic Medicine, Anhui Medical College, Hefei 230601, China.
Xiaoqing
X
Wang
Department of Orthopaedic, the First Affiliated Hospital of Anhui Medical University, Hefei 230031, China.
Gaoyuan
G
Wang
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China.
Zhicheng
Z
Wang
Department of Histology and Embryology, Anhui Medical University, Hefei 230032, China.
Xiaoyu
X
Chen
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology*; D001343:Autophagy; D002478:Cells, Cultured; D008928:Mitochondria / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D000070918:Synoviocytes / Q000187:drug effects* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000077185:Resveratrol