title: Interference of the apoptotic signaling pathway in RGC stress response by SP600125 in moderate ocular hypertensive rats.
abstract: The aim of the present study was to investigate the effect of SP600125 (1,9-pyrazoloanthrone), an inhibitor of JNK, on apoptosis of retinal ganglion cells (RGCs) induced by moderate elevation of intraocular pressure (IOP) in male rats. IOP was elevated by suture-pulley compression on eyeballs. Cell apoptosis, expression of phosphorylated JNK (p-JNK) and cleaved caspase-3 in retina were studied by TUNEL staining and immunohistochemistry. The expression of c-Jun in retina was assayed by Western blot. Following IOP elevation (about 45 mmHg) for 6 h, the number of TUNEL, p-JNK and cleaved caspase-3 positive cells and the amount of c-Jun expression in retina were significantly increased. All these changes were reversed by SP600125 treatment. The immune positive cells for TUNEL, p-JNK and cleaved caspase-3 following IOP elevation were localized at the RGC layer. We conclude that moderate elevation of IOP for 6 h induced apoptosis of RGCs, and SP600125 treatment attenuated this process by suppressing c-Jun expression.
authors.affiliation: Department of Physiology, Shandong University School of Medicine, Jinan 250012, Shandong, PR China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009798:Ocular Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology
chemical_list: D000873:Anthracenes; D004791:Enzyme Inhibitors; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3