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Norepinephrine protects against apoptosis of mesenchymal stem cells induced by high glucose
Authors:Yanan Kong  Liuhanghang Cheng  Li Ma  Haihong Li  Biao Cheng  Yu Zhao
Institution:1. Department of Plastic Surgery, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China;2. Department of Plastic Surgery and Burn Center, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China

Yanan Kong and Liuhanghang Cheng contributed equally to this work.;3. Department of Plastic Surgery and Burn Center, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China;4. Guangzhou School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People's Republic of China

Abstract:In diabetes, the number of bone mesenchymal stem cells (MSCs) decreases and their differentiation is impaired. However, the exact mechanism is unclear. Patients with diabetes often experience sympathetic nerve injury. Norepinephrine (NE), a major mediator of the sympathetic nervous system, influences rat MSC migration in culture and in vivo. The present study aimed to investigate the effect of NE on MSCs under high glucose conditions; therefore MSCs were treated with high glucose and NE. High glucose-induced MSCs apoptosis, which was reversed by NE. To verify the effect of NE, mice underwent sympathectomy and were used to establish a diabetic model. Diabetic mice with sympathectomy had a higher apoptosis rate and higher levels of reactive oxygen species in their bone marrow-derived cells than diabetic mice without sympathectomy. High glucose inhibited p-AKT production and B-Cell CLL/Lymphoma 2 expression, and promoted BAX and caspase-3 expression. NE reversed these effects of high glucose. An AKT inhibitor enhanced the effects of high glucose. Thus, NE had a protective effect on MSC apoptosis induced by high glucose, possibly via the AKT/BCL-2 pathway.
Keywords:apoptosis  diabetes mellitus  mesenchymal stem cells  norepinephrine
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