| Autophagy activation in the injured photoreceptor inhibits fas-mediated apoptosis. | |
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MedLine Citation:
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PMID: 21421874 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To examine the activation of autophagy and its relationship to Fas-mediated photoreceptor apoptosis during experimental retinal detachment. METHODS: Retina-retinal pigment epithelium (RPE) separation was created in Brown-Norway rats by subretinal injection of 1% hyaluronic acid and the intraretinal levels of the autophagy proteins LC3 and Atg5, the time course of LC3-I to LC3-II conversion, and the activation of cathepsins B and D were assayed with Western blot analysis and immunohistochemistry. We measured the ability of a Fas-activating antibody to induce LC3-I to LC3-II conversion in 661W cells, and the in vivo effect of Met12, a small molecule inhibitor of the Fas receptor, on LC3-I to LC3-II conversion and Atg5 expression. Autophagy activation was inhibited using 3-methyladenine (3-MA) or siRNA knockdown of Atg5 and the effect on apoptosis was measured using a caspase 8 activity assay, caspase 8 immunoblots, and photoreceptor TUNEL staining. RESULTS: Retina-RPE separation resulted in a Fas-dependent activation of autophagy, with increased Atg5 levels and intraphotoreceptor conversion of LC3-I to LC3-II. Detached retinas had increased levels of autophagosome-associated lysosomal proteases, cathepsins B and D. Inhibition of autophagy by 3-MA or siAtg5 accelerated the time course of caspase 8 activation and photoreceptor TUNEL staining. CONCLUSIONS: Autophagy activation occurs in the photoreceptors after retina-RPE separation. This appears to be, at least in part, dependent on Fas receptor activation, and plays a role in regulating the level of photoreceptor apoptosis. |
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Authors:
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Cagri G Besirli; Nicholas D Chinskey; Qiong-Duan Zheng; David N Zacks |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-06-13 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 52 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-06-14 Completed Date: 2011-08-23 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 4193-9 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan 48105-0714, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenine
/
analogs & derivatives,
pharmacology Animals Antigens, CD95 / metabolism* Apoptosis* / drug effects Autophagy* / drug effects Blotting, Western Caspase 8 / metabolism Cathepsin B / metabolism Cathepsin D / metabolism Cell Line Enzyme Activation / drug effects Immunohistochemistry Male Microtubule-Associated Proteins / metabolism Photoreceptor Cells, Vertebrate* Protein Isoforms / metabolism Proteins / genetics RNA, Small Interfering / pharmacology Rats Rats, Inbred BN Retinal Detachment / physiopathology* Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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NEI-EY-07003/EY/NEI NIH HHS; R01 EY020823-01/EY/NEI NIH HHS; R01-020823//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD95; 0/Atg5 protein, rat; 0/LC3 protein, rat; 0/Microtubule-Associated Proteins; 0/Protein Isoforms; 0/Proteins; 0/RNA, Small Interfering; 5142-23-4/3-methyladenine; 73-24-5/Adenine; EC 3.4.22.-/Casp8 protein, rat; EC 3.4.22.-/Caspase 8; EC 3.4.22.1/Cathepsin B; EC 3.4.22.1/Ctsb protein, rat; EC 3.4.23.5/Cathepsin D; EC 3.4.23.5/Ctsd protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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