title: Ischemic preconditioning-induced neuroprotection against transient cerebral ischemic damage via attenuating ubiquitin aggregation.
abstract: Ubiquitin binds to short-lived proteins, and denatured proteins are produced by various forms of injuries. In the present study, we investigated the effect of ischemic preconditioning (IPC) on free ubiquitin and its mutant form (ubiquitin(+1)) in the gerbil hippocampus induced by transient cerebral ischemia. The animals were randomly assigned to 4 groups (sham-operated-group, ischemia-operated-group, IPC plus (+)-sham-operated-group, and IPC+ischemia-operated-group). IPC was induced by subjecting gerbils to a 2 min of ischemia followed by 1 day of recovery. A significant loss of neurons was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) in the ischemia-operated-groups 5 days after ischemia-reperfusion (I-R). In all the IPC+ischemia-operated-groups, neurons in the SP were well protected. We found that strong ubiquitin immunoreactivity was detected in the SP in the sham-operated-group and the immunoreactivity was decreased with time after I-R. In all the IPC+ischemia-operated-groups, ubiquitin immunoreactivity in the SP was similar to that in the sham-operated group. Moderate ubiquitin(+1) immunoreactivity was detected in the SP of the sham-operated-group, and the immunoreactivity was markedly increased 2 days after I-R. Five days after I-R, ubiquitin(+1) immunoreactivity was very weak in the SP. In all the IPC+ischemia-operated-groups, ubiquitin(+1) immunoreactivity in the SP was slightly decreased with time after I-R. Western blot analysis showed that, in all the IPC+ischemia-ischemia-groups, the levels of ubiquitin and ubiquitin(+1) proteins were well maintained after I-R. In brief, our findings suggest that the inhibition of the depletion of free ubiquitin and the formation of ubiquitin(+1) may have an essential role in inducing cerebral ischemic tolerance by IPC.
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701 South Korea.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701 South Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Neuroscience, College of Medicine, Korea University, Seoul 136-705, South Korea.
authors.forename: Geum-Sil
authors.initials: GS
authors.lastname: Cho
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701 South Korea.
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701 South Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Institute of Integrative traditional & Western Medicine, Medical College, Yangzhou University, Yangzhou 25001, China.
authors.forename: Bing Chun
authors.initials: BC
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology, Kangwon National University Hospital, Chuncheon 200-701, South Korea.
authors.forename: Hyuk Min
authors.initials: HM
authors.lastname: Kwon
authors.affiliation: Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Cheon
authors.affiliation: Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea; Institute of Medical Sciences, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Jun Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Institute of Medical Sciences, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea; Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Hui Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701 South Korea; Institute of Medical Sciences, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea. Electronic address: mhwon@kangwon.ac.kr.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.affiliation: Department of Emergency Medicine, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon 200-702, South Korea. Electronic address: siris94@hanmail.net.
authors.forename: Jeong Yeol
authors.initials: JY
authors.lastname: Seo
mesh_terms: D000818:Animals; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology; D025801:Ubiquitin / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D025801:Ubiquitin
keywords: Delayed neuronal death; Hippocampus; Ischemia–reperfusion; Ischemic preconditioning; Pyramidal neurons; Ubiquitin system