title: Metformin Protects Neurons against Oxygen-Glucose Deprivation/Reoxygenation -Induced Injury by Down-Regulating MAD2B.
abstract: OBJECTIVE
  Metformin, the common medication for type II diabetes, has protective effects on cerebral ischemia. However, the molecular mechanisms are far from clear. Mitotic arrest deficient 2-like protein 2 (MAD2B), an inhibitor of the anaphase-promoting complex (APC), is widely expressed in hippocampal and cortical neurons and plays an important role in mediating high glucose-induced neurotoxicity. The present study investigated whether metformin modifies the expression of MAD2B and to exert its neuroprotective effects in primary cultured cortical neurons during oxygen-glucose deprivation/reoxygenation (OGD/R), a widely used in vitro model of ischemia/reperfusion.
  
  
  METHODS
  Primary cortical neurons were cultured, deprived of oxygen-glucose for 1 h, and then recovered with oxygen-glucose for 12 h and 24 h. Cell viability was measured by detecting the levels of lactate dehydrogenase (LDH) in culture medium. The levels of MAD2B, cyclin B and p-histone 3 were measured by Western blot.
  
  
  RESULTS
  Cell viability of neurons was reduced under oxygen-glucose deprivation/reoxygenation (OGD/R). The expression of MAD2B was increased under OGD/R. The levels of cyclin B1, which is a substrate of APC, were also increased. Moreover, OGD/R up-regulated the phosphorylation levels of histone 3, which is the induction of aberrant re-entry of post-mitotic neurons. However, pretreatment of neurons with metformin alleviated OGD/R-induced injury. Metformin further decreased the expression of MAD2B, cyclin B1 and phosphorylation levels of histone 3.
  
  
  CONCLUSIONS
  Metformin exerts its neuroprotective effect through regulating the expression of MAD2B in neurons under OGD/R.
authors.affiliation: Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xianfang
authors.initials: X
authors.lastname: Meng
authors.forename: Guangpin
authors.initials: G
authors.lastname: Chu
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Qiu
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Chen
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Peng
authors.forename: Chen
authors.initials: C
authors.lastname: Ye
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: He
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D056744:Cyclin B1 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D005947:Glucose / Q000172:deficiency*; D064246:Mad2 Proteins / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology*; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000066829:Neuroprotection / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity; D010100:Oxygen / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D016196:S Phase / Q000187:drug effects
chemical_list: D056744:Cyclin B1; D064246:Mad2 Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D008687:Metformin; D005947:Glucose; D010100:Oxygen