title: Cdh1 inhibits reactive astrocyte proliferation after oxygen-glucose deprivation and reperfusion.
abstract: Anaphase-promoting complex (APC) and its co-activator Cdh1 are required for cell cycle regulation in proliferating cells. Recent studies have defined diverse functions of APC-Cdh1 in nervous system development and injury. Our previous studies have demonstrated the activity of APC-Cdh1 is down-regulated in hippocampus after global cerebral ischemia. But the detailed mechanisms of APC-Cdh1 in ischemic nervous injury are unclear. It is known that astrocyte proliferation is an important pathophysiological process following cerebral ischemia. However, the role of APC-Cdh1 in reactive astrocyte proliferation is not determined yet. In the present study, we cultured primary cerebral astrocytes and set up in vitro oxygen-glucose deprivation and reperfusion model. Our results showed that the expression of Cdh1 was decreased while Skp2 (the downstream substrate of APC-Cdh1) was increased in astrocytes after 1h oxygen-glucose deprivation and reperfusion. The down-regulation of APC-Cdh1 was coupled with reactive astrocyte proliferation. By constructing Cdh1 expressing lentivirus system, we also found exogenous Cdh1 can down-regulate Skp2 and inhibit reactive astrocyte proliferation induced by oxygen-glucose deprivation and reperfusion. Moreover, Western blot showed that other downstream proteins of APC-Cdh1, PFK-1 and SnoN, were decreased in the inhibition of reactive astrocyte proliferation with Cdh1 expressing lentivirus treatment. These results suggest that Cdh1 plays an important role in the regulation of reactive astrocyte proliferation induced by oxygen-glucose deprivation and reperfusion.
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Qiu
authors.forename: Chuanhan
authors.initials: C
authors.lastname: Zhang
authors.forename: Youyou
authors.initials: Y
authors.lastname: Lv
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chang
authors.initials: C
authors.lastname: Zhu
authors.forename: Xueren
authors.initials: X
authors.lastname: Wang
authors.forename: Wenlong
authors.initials: W
authors.lastname: Yao
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D064200:Cdh1 Proteins / Q000502:physiology*; D049109:Cell Proliferation; D005947:Glucose / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
chemical_list: D064200:Cdh1 Proteins; D005947:Glucose; D010100:Oxygen