title: Ischemia-related changes in naive and mutant forms of ubiquitin and neuroprotective effects of ubiquitin in the hippocampus following experimental transient ischemic damage.
abstract: Ubiquitin binds to short-lived proteins and denatured proteins produced by various forms of injury. The loss of ubiquitin leads to an accumulation of abnormal proteins and may affect cellular structure and function. The aim of the present study is to observe the chronological changes in ubiquitin naive form and its mutant form (ubiquitin(+1)) in the hippocampal CA1 region (CA1) after transient cerebral ischemia in gerbils. Delayed neuronal death in the CA1 was confirmed 4 days after ischemic insult with NeuN immunohistochemistry. Ubiquitin immunoreactivity and protein level in the CA1 were lowest at 12 h after ischemia/reperfusion; thereafter, they were increased with time. Ubiquitin(+1) immunoreactivity and protein levels in the CA1 were slightly decreased at 3 h after ischemia/reperfusion, and they were significantly increased 1 day after ischemia/reperfusion. In addition, ubiquitin and ubiquitin(+1) immunoreaction was expressed in astrocytes after delayed neuronal death in the ischemic CA1. To elucidate the protective effect of ubiquitin on ischemic damage, the animals were treated with ubiquitin (1.5 mg/kg body weight) intravenously via the femoral vein. Ubiquitin treatment significantly reduced ischemia-induced locomotor hyperactivity, neuronal death and reactive gliosis such as astrocytes and microglia. In addition, 5 days after ubiquitin treatment in the ischemic group, ubiquitin immunoreactivity was similar to that in the ubiquitin-treated sham group, however, ubiquitin(+1) immunoreactivity was higher than that in the ubiquitin-treated sham group. These findings indicate that the depletion of ubiquitin and the accumulation of ubiquitin(+1) in CA1 pyramidal neurons after transient cerebral ischemia may inhibit ubiquitin proteolytic pathway and this leads to delayed neuronal death of CA1 pyramidal neurons directly or indirectly after transient cerebral ischemia.
authors: Department of Emergency Medicine, Hallym University, College of Medicine, Hallym University Sacred Heart Hospital, Pyeongchon 431-070, South Korea.
authors: Hee Cheol
authors: HC
authors: Ahn
authors: Ki-Yeon
authors: KY
authors: Yoo
authors: In Koo
authors: IK
authors: Hwang
authors: Jun Hwi
authors: JH
authors: Cho
authors: Choong Hyun
authors: CH
authors: Lee
authors: Jung Hoon
authors: JH
authors: Choi
authors: Hua
authors: H
authors: Li
authors: Byung Ryul
authors: BR
authors: Cho
authors: Young-Myeong
authors: YM
authors: Kim
authors: Moo-Ho
authors: MH
authors: Won
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D005849:Gerbillinae; D005911:Gliosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D054875:Ubiquitination / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D025801:Ubiquitin