title: PTEN deletion prevents ischemic brain injury by activating the mTOR signaling pathway.
abstract: It is increasingly clear that the tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a negative regulator of neuronal cell survival. However, its molecular mechanisms remain poorly understood. Here we found that PTEN/mTOR is critical for controlling neuronal cell death after ischemic brain injury. Male rats were subjected to MCAO (middle cerebral artery occlusion) followed by pretreating with bpv (pic), a potent inhibitor for PTEN, or by intra-cerebroventricular infusion of PTEN siRNA. bpv (pic) significantly decreased infarct volume and reduced the number of TUNEL-positive cells. We further demonstrated that although bpv (pic) did not affect brain injury-induced mTOR protein expression, bpv (pic) prevented decrease in phosphorylation of mTOR, and the subsequent decrease in S6. Similarly, down-regulation of PTEN expression also reduced the number of TUNEL-positive cells, and increased phospho-mTOR. These data suggest that PTEN deletion prevents neuronal cell death resulting from ischemic brain injury and that its neuroprotective effects are mediated by increasing the injury-induced mTOR phosphorylation.
authors.affiliation: Department of Orthopaedics Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.
authors.forename: G D
authors.initials: GD
authors.lastname: Shi
authors.forename: Y P
authors.initials: YP
authors.lastname: OuYang
authors.forename: J G
authors.initials: JG
authors.lastname: Shi
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: W
authors.initials: W
authors.lastname: Yuan
authors.forename: L S
authors.initials: LS
authors.lastname: Jia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D020520:Brain Infarction / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002545:Brain Ischemia / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D017353:Gene Deletion; D008297:Male; D009474:Neurons / Q000201:enzymology / Q000473:pathology*; D009942:Organometallic Compounds / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D009942:Organometallic Compounds; C119540:oxodiperoxo(pyridine-2-carboxylate)vanadate(V); C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat