title: HSP70, the earliest-induced gene in the zebrafish retina during optic nerve regeneration: its role in cell survival.
abstract: Fish retinal ganglion cells (RGCs) can survive and regrow their axons after optic nerve injury. Injured RGCs express anti-apoptotic proteins, such as Bcl-2, after nerve injury; however, upstream effectors of this anti-apoptotic protein are not yet fully understood. Heat shock proteins (HSPs) play a crucial role in cell survival against various stress conditions. In this study, we focused on HSP70 expression in the zebrafish retina after optic nerve injury. HSP70 mRNA and protein levels increased rapidly 2.3-fold in RGCs by 1-6 h after injury and returned to control levels by 1-3 days. HSP70 transcription is regulated by heat shock factor 1 (HSF1). HSF1 mRNA and phosphorylated-HSF1 protein rapidly increased by 2.2-fold in RGCs 0.5-6 h after injury. Intraocular injection of HSP inhibitor I significantly suppressed the induction of HSP70 expression after nerve injury. It also suppressed Bcl-2 protein induction and resulted in TUNEL-positive cell death of RGCs at 5 days post-injury. Zebrafish treated with HSP inhibitor I retarded axonal elongation or visual function after injury, as analyzed by GAP43 expression and behavioral analysis of optomotor response, respectively. These results strongly indicate that HSP70, the earliest induced gene in the zebrafish retina after optic nerve injury, is a crucial factor for RGCs survival and optic nerve regeneration in fish.
authors.affiliation: Division of Health Sciences, Graduate School of Medicine, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Nagashima
authors.forename: Chieko
authors.initials: C
authors.lastname: Fujikawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mawatari
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Mori
authors.forename: Satoru
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D009416:Nerve Regeneration / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology*; D020221:Optic Nerve Injuries / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000096:biosynthesis*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D029961:Zebrafish Proteins