Effect of oxidative stress-induced autophagy on proliferation and apoptosis of MSCs |
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Authors: | LIU Guan-yu HE Wei-yang ZHU Xin YANG Fan HUANG Xiao-long YIN Hu-bin GOU Xin |
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Institution: | 1. Department of Urinary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;
2. Chongqing Key Laboratory of Molecular Oncology and Epigenetics, Chongqing 400016, China |
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Abstract: | AIM: To investigate whether oxidative stress is able to induce autophagy in mesenchymal stem cells (MSCs), and to explore the effects of autophagy on MSC proliferation and apoptosis under oxidative stress circumstance as well as the underlying mechanism for promoting the therapeutic effects of transplanted MSCs on treating diabetes mellitus erectile dysfunction (DMED). METHODS: Hydrogen peroxide (H2O2) was applied to simulate the oxidative stress circumstance. The effects of H2O2 at concentration of 0, 50, 100, 200, 400 μmol/L on the viability of MSCs were tested by the method of Trypan blue exclusion and MTT assay respectively . The methods of MTT assay, Western blot and transmission electron microscope (TEM) were used to explore the effects of H2O2 on MSC apoptosis and autophagy. RESULTS: The proliferation of MSCs was obviously inhibited by H2O2 in a dose-dependent manner (P<0.01) and the 50% inhibiting concentration (IC50) was (384.58±16.89) μmol/L. H2O2 induced apoptosis and autophay of MSCs. The proliferation rate of MSCs was suppressed by H2O2 significantly (P<0.05), with a further decline by blockade of autophagy (P<0.05) whereas increased by blockade of apoptosis (P<0.05). H2O2 induced MSCs apoptosis obviously (P<0.05), with an augment of apoptosis (P<0.05) by blockade of autophagy. Furthermore, the H2O2 increased expression of cleaved caspase-3 and cleavage of poly ADP-ribose polymerase 1 (PARP1), Which were decreased by apoptosis blockade whereas were enhanced by blockade of autopahgy. CONCLUSION: Oxidative stress plays a dual role in MSC survival, which induces MSC apoptosis and autophagy. Moreover, blockade of autophagy intensifies MSC apoptosis. Therefore, it is a promising method to ameliorate the effects of stem-cell based therapy on DMED by enhancing protective autophagy to increase the survival rate of transplanted MSCs against oxidative stress circumstance caused by diabetes mellitus. |
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Keywords: | Autophagy Mesenchymal stem cells Cell proliferation Apoptosis Oxidative stress |
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