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Overexpressed mutant optineurin(E50K) induces retinal ganglion cells apoptosis via the mitochondrial pathway
- Source :
- Molecular biology reports. 39(5)
- Publication Year :
- 2011
-
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.
- Subjects :
- Retinal Ganglion Cells
Programmed cell death
Mutant
Blotting, Western
Intracellular Space
Apoptosis
Cell Cycle Proteins
Biology
Mitochondrion
Cell Fractionation
Retinal ganglion
Cell Line
Transcription Factor TFIIIA
Genetics
Animals
Humans
Molecular Biology
Optineurin
Membrane Potential, Mitochondrial
Staining and Labeling
Membrane Transport Proteins
General Medicine
Transfection
Flow Cytometry
Molecular biology
Cell biology
Mitochondria
Rats
Cytosol
Amino Acid Substitution
Microscopy, Fluorescence
Mutant Proteins
Reactive Oxygen Species
Propidium
Signal Transduction
Subcellular Fractions
Subjects
Details
- ISSN :
- 15734978
- Volume :
- 39
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecular biology reports
- Accession number :
- edsair.doi.dedup.....e5cbcc4d53ee0d6d2565cb27f92c87d7