title: The p53-independent nuclear translocation of cyclin G1 in degenerating neurons by ischemic and traumatic insults.
abstract: Cyclin G1 (CG1) was identified as a p53-transactivated target gene, and yet its physiological and pathological roles have been unclear. Here, we demonstrate that CG1 is translocated from cytoplasm to the nuclei of neurons in response to variety of injuries. In the normal matured rodent brain, CG1 immunoreactivity was hardly observed; however, some brain injuries exhibited intense CG1 immunoreactivity in the nuclei of the damaged neurons. Transient common carotid artery occlusion (CCAO) in the gerbil showed strong CG1-like immunoreactivity in the hippocampal CA1 neurons, and permanent middle cerebral artery occlusion (MCAO) in the mouse showed strong CG1-like immunoreactivity in the nuclei of neurons located in the ischemic brain regions. TUNEL staining did not exactly overlap with the CG1-positive cells, but overlapped highly with Fluoro-Jade B staining, a degeneration marker. Brain trauma caused by knife cut, cold injury, and kinate injection also showed CG1 accumulation in the neuronal nuclei located near the injury site. These observations were obtained in p53-deficient mice as well, suggesting that the accumulation of CG1 in the injured neurons is p53-independent. A similar nuclear translocation of endogenous CG1 was confirmed in a primary culture of cortical neurons when a toxic level of N-methyl-D-aspartate (NMDA) was applied. These results demonstrate that nuclear translocation of CG1 from cytoplasmic region occurs in damaged and degenerating neurons in a p53-independent manner, and the CG1 nuclear staining could be a good marker for the neurons received fatal damages.
authors.affiliation: Department of Anatomy, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Maeda
authors.forename: Kei-Ichi
authors.initials: K
authors.lastname: Ampo
authors.forename: Sumiko
authors.initials: S
authors.lastname: Kiryu-Seo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konishi
authors.forename: Norihiro
authors.initials: N
authors.lastname: Ohba
authors.forename: Chiho
authors.initials: C
authors.lastname: Kadono
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyama
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005452:Fluoresceins; D005456:Fluorescent Dyes / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005849:Gerbillinae; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron / Q000379:methods; D016202:N-Methylaspartate / Q000494:pharmacology; D009410:Nerve Degeneration / Q000209:etiology* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009930:Organic Chemicals; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000502:physiology*
chemical_list: C534703:Ccng1 protein, mouse; C534704:Ccng1 protein, rat; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; D018690:Excitatory Amino Acid Agonists; D005452:Fluoresceins; D005456:Fluorescent Dyes; D009930:Organic Chemicals; D011500:Protein Synthesis Inhibitors; D016159:Tumor Suppressor Protein p53; C435731:fluoro jade; D016202:N-Methylaspartate; D003513:Cycloheximide; D010751:Phosphopyruvate Hydratase; D007608:Kainic Acid