title: Overexpressed mutant optineurin(E50K) induces retinal ganglion cells apoptosis via the mitochondrial pathway.
abstract: Mutations in the coding region of the OPTN gene are associated with certain glaucomas. Although the function of the optineurin protein is yet to be elucidated, the most common mutation, E50K, is associated with a severe phenotype. Plasmids expressing wild-type Optineurin (WT) and mutant Optineurin(E50K) were transfected into RGC-5 and monitored by immunofluorescence staining and western blotting. The mutant Optineurin(E50K) induced the death of retinal ganglion cells by generation of reactive oxygen species accompanied disruption of mitochondrial transmembrane potential, down-regulation of bcl-2, and up-regulation of bax, which led to the release of cytochrome C from the mitochondria into the cytosol, which, in turn, resulted in the activation of caspase-9 and caspase-3, indicating that mutant Optineurin(E50K) acquired the ability to induce cell death through the mitochondrial caspase-dependent cell death pathway.
authors.affiliation: Eye Hospital, First Affiliated Hospital of Harbin Medical University, Key Laboratory of Ophthalmology, No. 23 Youzheng Street, Harbin, Heilongjiang, 150001, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Meng
authors.forename: Jia
authors.initials: J
authors.lastname: Lv
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ge
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Xue
authors.forename: Yuanmao
authors.initials: Y
authors.lastname: Zhu
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D002458:Cell Fractionation; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D026901:Membrane Transport Proteins; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism*; D011419:Propidium / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D013194:Staining and Labeling; D013347:Subcellular Fractions / Q000378:metabolism; D035582:Transcription Factor TFIIIA / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; D050505:Mutant Proteins; C409460:OPTN protein, human; D017382:Reactive Oxygen Species; D035582:Transcription Factor TFIIIA; D011419:Propidium