Drug Design, Development and Therapy (Apr 2020)
Metformin Inhibits Propofol-Induced Apoptosis of Mouse Hippocampal Neurons HT-22 Through Downregulating Cav-1
Abstract
Jianyun Ge,1,* Yulin Huang,2,* Yi Zhang,3 Lin Liu,1 Tianyu Gu,1 Xu Liu,1 Lei Yao,1 Mengmeng Cai,1 Jiafeng Sun,1 Jie Song1 1Department of Anesthesiology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People’s Republic of China; 2Department of Anesthesiology, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, Jiangsu 210000, People’s Republic of China; 3Department of Neurosurgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie SongDepartment of Anesthesiology, The Second Affiliated Hospital of Nantong University, No. 6 North Haier Lane Road, Nantong 226001, Jiangsu, People’s Republic of ChinaEmail [email protected]: To elucidate the neuroprotective function of metformin in suppressing propofol-induced apoptosis of HT-22 cells.Methods: HT-22 cells were treated with 0, 10 or 100 μmol/L propofol, followed by determination of their proliferative ability. Subsequently, changes in proliferation and apoptosis of propofol-treated HT-22 cells induced with metformin were assessed. Apoptosis-associated genes in HT-22 cells were detected by Western blot. At last, regulatory effects of Cav-1 on propofol and metformin-treated HT-22 cells were examined.Results: Propofol treatment dose-dependently decreased proliferative ability and increased apoptosis ability in HT-22 cells, which were partially blocked by metformin administration. Upregulated Bcl-2 and downregulated Bax were observed in propofol-treated HT-22 cells following metformin administration. In addition, Cav-1 level in HT-22 cells was regulated by metformin treatment. Notably, metformin reversed propofol-induced apoptosis stimulation and proliferation decline in HT-22 cells via downregulating Cav-1.Conclusion: In our study, we found that propofol could induce apoptosis of HT-22 cells and metformin could rescue the apoptosis effect regulated by propofol. Then, we found that metformin protects propofol-induced neuronal apoptosis via downregulating Cav-1.Keywords: metformin, propofol, Cav-1, apoptosis
