Abstract | PURPOSE: METHODS: RESULTS: Treatment with tunicamycin at 1, 2, and 4 microg/mL for 24 hours increased the number of YO-PRO-1 and PI-positive (apoptosis or necrosis indicator) cells in a concentration-dependent manner. Immunoblotting analysis showed that tunicamycin at 2 microg/mL induced BiP, ATF4, and CHOP protein production and PKR phosphorylation. Both the PKR inhibitor (0.03-1 microM) and the PKR knockdown (using siRNA) inhibited tunicamycin-induced RGC-5 cell death. The same inhibitor also reduced NMDA-induced retinal damage in vivo. The PKR inhibitor reduced the tunicamycin-induced increase in CHOP but not that in BiP protein production. CONCLUSIONS: These results indicate that inhibiting PKR activation is neuroprotective against ER stress-induced retinal damage, suggesting that PKR activation may be involved in the mechanisms underlying ER stress-induced cell death.
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Authors | Masamitsu Shimazawa, Yasushi Ito, Yuta Inokuchi, Hideaki Hara |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 48
Issue 8
Pg. 3729-36
(Aug 2007)
ISSN: 0146-0404 [Print] United States |
PMID | 17652745
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antiviral Agents
- Excitatory Amino Acid Agonists
- GRP78 protein, rat
- Heat-Shock Proteins
- Molecular Chaperones
- RNA, Small Interfering
- Tunicamycin
- Transcription Factor CHOP
- N-Methylaspartate
- eIF-2 Kinase
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Topics |
- Animals
- Animals, Outbred Strains
- Antiviral Agents
(toxicity)
- Apoptosis
(drug effects, physiology)
- Cell Line, Transformed
- Endoplasmic Reticulum
(drug effects, enzymology)
- Excitatory Amino Acid Agonists
(toxicity)
- Heat-Shock Proteins
(metabolism)
- Mice
- Molecular Chaperones
(metabolism)
- N-Methylaspartate
(toxicity)
- Phosphorylation
(drug effects)
- RNA, Small Interfering
- Rats
- Retinal Ganglion Cells
(drug effects, enzymology, pathology)
- Transcription Factor CHOP
(metabolism)
- Tunicamycin
(toxicity)
- eIF-2 Kinase
(antagonists & inhibitors, genetics, metabolism)
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