title: Regulation on Beclin-1 expression by mTOR in CoCl2-induced HT22 cell ischemia-reperfusion injury.
abstract: It has been reported that cerebral ischemia/reperfusion (I/R) injury can activate autophagy. However, the role of autophagy in cerebral I/R injury remains controversy. Two major proteins, mTOR and Beclin-1, govern the formation of autophagosomes to regulate autophagy activity. However, the cross-talking between Beclin-1 and mTOR in cerebral I/R injury remains elusive. In this study, global cerebral I/R injury animal model and focal cerebral I/R injury animal model were induced to test the variation of Beclin-1 level in vivo. To further confirm the variation of Beclin-1 level and investigate the cross-talking between Beclin-1 and mammalian target of rapamycin (mTOR) in I/R injury, we used cobalt chloride (CoCl2) to develop an I/R injury cell model in HT22 cell line. Our data showed that the levels of Beclin-1 and phosphorylated mammalian target of rapamycin (p-mTOR) were clearly induced by I/R injury in vitro. And the time course studies suggested that the Beclin-1 and mTOR may have coordinated regulation in ischemia stages but not in reperfusion stages. Moreover, inhibitor of mTOR could prevent Beclin-1 decreasing, but this prevention may play opposite roles in different stages of I/R injury. We conclude that this study represents a major advance in our understanding of the cross-talking of two key proteins, Beclin-1 and mTOR, in autophagy and the role of autophagy in cerebral I/R injury.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta West Road, Xi'an, Shaanxi 710061, PR China; Department of Neurosurgery, Ankang City Central Hospital, Ankang, Shaanxi 725000, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta West Road, Xi'an, Shaanxi 710061, PR China; Department of Neurosurgery, Ankang City Central Hospital, Ankang, Shaanxi 725000, PR China.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Ankang City Central Hospital, Ankang, Shaanxi 725000, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta West Road, Xi'an, Shaanxi 710061, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta West Road, Xi'an, Shaanxi 710061, PR China.
authors.forename: Ge
authors.initials: G
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta West Road, Xi'an, Shaanxi 710061, PR China. Electronic address: maodewang2015@163.com.
authors.forename: Maode
authors.initials: M
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000071186:Beclin-1; D002545:Brain Ischemia / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival; D003035:Cobalt / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000139:chemically induced*; D020123:Sirolimus / Q000633:toxicity*
chemical_list: D016587:Antimutagenic Agents; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; D003035:Cobalt; C018021:cobaltous chloride; D020123:Sirolimus
keywords: Autophagy; Beclin-1; Ischemia; Reperfusion; mTOR