Effect of metformin on Schwann cells under hypoxia condition.
Metformin, which is the first-line drug for the treatment of diabetes mellitus type 2, has been proved to possess beneficial effects on nerve regeneration in many studies. However, the underlying mechanism is currently unclear. The present study was designed to investigate the potential beneficial effect of metformin on SCs under hypoxia condition, which is a biological process at the injury site. The cell number and cell viability of SCs were examined using fluorescence observation and MTT assay. The migration of SCs was evaluated using a Transwell chamber. The expression and secretion of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF) and neural cell adhesion molecule (N-CAM) in SCs were assayed by RT-PCR and ELISA method. The results showed that metformin could help SCs recover from hypoxia injury and inhibit hypoxia-induced apoptosis. In addition, metformin could partially reverse the detrimental effect of hypoxia on cell number, viability, migration and adhesion. Metformin is also capable of maintaining the biological activities of SCs after hypoxia injury, such as increasing the expression and secretion of BDNF, NGF, GDNF, and N-CAM. Further studies showed that pre-incubation with AMPK (5'-AMP-activated protein kinase) inhibitor Compound C might partially inhibit the effect of metformin mentioned above, indicating the possible involvement of AMPK pathway in the beneficial effects of metformin on peripheral nervous system. In conclusion, metformin is capable of alleviating hypoxia-induced injury to SCs and AMPK pathway might be involved in this process.
Department of Orthopedics, General Hospital of Shenyang Military Area Command of Chinese PLA, Rescue Center of Severe Wound and Trauma of Chinese PLA Shenyang 110016, Liaoning, China.
Junxiong
J
Ma
Department of Orthopedics, General Hospital of Shenyang Military Area Command of Chinese PLA, Rescue Center of Severe Wound and Trauma of Chinese PLA Shenyang 110016, Liaoning, China.
Jun
J
Liu
Department of Orthopedics, General Hospital of Shenyang Military Area Command of Chinese PLA, Rescue Center of Severe Wound and Trauma of Chinese PLA Shenyang 110016, Liaoning, China.
Hailong
H
Yu
Department of Orthopedics, General Hospital of Shenyang Military Area Command of Chinese PLA, Rescue Center of Severe Wound and Trauma of Chinese PLA Shenyang 110016, Liaoning, China.
Yu
Y
Chen
Department of Orthopedics, General Hospital of Shenyang Military Area Command of Chinese PLA, Rescue Center of Severe Wound and Trauma of Chinese PLA Shenyang 110016, Liaoning, China.
Qi
Q
Wang
Department of Orthopedics, General Hospital of Shenyang Military Area Command of Chinese PLA, Rescue Center of Severe Wound and Trauma of Chinese PLA Shenyang 110016, Liaoning, China.
Liangbi
L
Xiang
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D015687:Cell Hypoxia; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D019006:Neural Cell Adhesion Molecules; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D008687:Metformin; D055372:AMP-Activated Protein Kinases
AMPK; Metformin; Schwann cell; hypoxia