PMID- 25896938 OWN - NLM STAT- MEDLINE DCOM- 20160222 LR - 20161125 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1614 DP - 2015 Jul 21 TI - Regulation on Beclin-1 expression by mTOR in CoCl2-induced HT22 cell ischemia-reperfusion injury. PG - 60-6 LID - S0006-8993(15)00305-4 [pii] LID - 10.1016/j.brainres.2015.04.016 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Yang, Tao AU - Yang T AD - 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. FAU - Li, Dongbo AU - Li D AD - 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. FAU - Liu, Feng AU - Liu F AD - Department of Neurosurgery, Ankang City Central Hospital, Ankang, Shaanxi 725000, PR China. FAU - Qi, Lei AU - Qi L AD - Department of Neurosurgery, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta West Road, Xi'an, Shaanxi 710061, PR China. FAU - Yan, Ge AU - Yan G AD - Department of Neurosurgery, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta West Road, Xi'an, Shaanxi 710061, PR China. FAU - Wang, Maode AU - Wang M AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150418 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Antimutagenic Agents) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Beclin-1) RN - 0 (Becn1 protein, rat) RN - 3G0H8C9362 (Cobalt) RN - EVS87XF13W (cobaltous chloride) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Analysis of Variance MH - Animals MH - Antimutagenic Agents/*pharmacology MH - Apoptosis Regulatory Proteins/*metabolism MH - Beclin-1 MH - Brain Ischemia/pathology MH - Cell Line MH - Cell Survival MH - Cobalt/*pharmacology MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Gene Expression Regulation/*drug effects MH - Male MH - Mice MH - *Neurons/drug effects/metabolism/pathology MH - Phosphorylation MH - Rats MH - Rats, Sprague-Dawley MH - Reperfusion Injury/*chemically induced MH - Sirolimus/*toxicity OTO - NOTNLM OT - Autophagy OT - Beclin-1 OT - Ischemia OT - Reperfusion OT - mTOR EDAT- 2015/04/22 06:00 MHDA- 2016/02/24 06:00 CRDT- 2015/04/22 06:00 PHST- 2015/01/20 00:00 [received] PHST- 2015/03/25 00:00 [revised] PHST- 2015/04/09 00:00 [accepted] PHST- 2015/04/22 06:00 [entrez] PHST- 2015/04/22 06:00 [pubmed] PHST- 2016/02/24 06:00 [medline] AID - S0006-8993(15)00305-4 [pii] AID - 10.1016/j.brainres.2015.04.016 [doi] PST - ppublish SO - Brain Res. 2015 Jul 21;1614:60-6. doi: 10.1016/j.brainres.2015.04.016. Epub 2015 Apr 18.