title: Neuroprotective effect of protease-activated receptor-2 in the hypoxia-induced apoptosis of rat RGC-5 cells.
abstract: Hypoxia-induced apoptosis of retinal ganglion cells (RGCs) is regarded as a pivotal pathological process in various ocular diseases. Protease-activated receptor-2 (PAR-2) is involved in the regulation of cell inflammation, differentiation, and apoptosis in many cell types and tissues, but the role of PAR-2 in RGCs under pathological conditions remains unknown. The purpose of this study was to investigate the role of PAR-2 in the apoptosis of RGCs under hypoxic stress. An immortalized rat RGC line (RGC-5) was exposed to hypoxia (5 % O₂). The expression and location of PAR-2 in RGC-5 cells under hypoxia stress were investigated using real-time PCR, western blotting and immunocytochemistry. Cell viability was determined using the Cell Counting Kit-8 assay. Apoptosis was detected using Hoechst 33342 staining and AnnexinV-FITC/PI assays. The role of Bcl-2, Bax, and the active subunit of caspase-3 was also investigated. The results showed that PAR-2 was functionally expressed in RGC-5 cells and up-regulated at both mRNA and protein levels under hypoxic stress. The PAR-2 selective agonist, SLIGRL, rescued RGC-5 cells from hypoxia-induced apoptosis through up-regulation of the Bcl-2/Bax ratio and down-regulation of caspase-3 activation. This study provides the first evidence that PAR-2 has a protective effect against the hypoxia-induced apoptosis of RGC-5 cells.
authors.affiliation: Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Peng
authors.forename: Jiaping
authors.initials: J
authors.lastname: Zhang
authors.forename: Haiwei
authors.initials: H
authors.lastname: Xu
authors.forename: Jianrong
authors.initials: J
authors.lastname: He
authors.forename: Xi
authors.initials: X
authors.lastname: Ying
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival; D021381:Protein Transport; D051381:Rats; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D044464:Receptor, PAR-2