| Oxidative-induced apoptosis to an immortalized ganglion cell line is caspase independent but involves the activation of poly(ADP-ribose)polymerase and apoptosis-inducing factor. | |
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MedLine Citation:
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PMID: 18053973 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The aim of the present work was to characterize the molecular basis of oxidative-induced death, a process that has been implicated in eye diseases like glaucoma, in RGC-5 cells, an immortalized retinal ganglion cell (RGC) line. Oxidative stress was induced by treatment of RGC-5 cells with hydrogen peroxide and compared to a known effect of a light insult (1000 lx, 400-760 nm). Hydrogen peroxide causes a loss of viability of RGC-5 cells in a dose-dependent manner. Loss of cell viability was by apoptosis characterized by breakdown of DNA (TUNEL method), presence of membrane phosphatidylserine (APOPercentage method), activation of PARP-1 and AIF. Oxidative stress caused a stimulation of ROS which reached maximum levels before optimum apoptosis. Hydrogen-peroxide-induced apoptosis did not result in an activation of caspase-3 and was unaffected by the caspase inhibitor Z-VAD-fmk. However, the PARP-1 inhibitor NU-1025 counteracted the effects of hydrogen peroxide and light. Evidence is provided to show that both forms of oxidative stress caused AIF to be cleaved with the product located to the cytosolic compartment. Light-induced apoptosis was attenuated by the presence of the mitochondrial uncoupler M3778 but potentiated by the presence of cobalt. In contrast, hydrogen-peroxide-induced apoptosis was unaffected by M3778 but attenuated by cobalt. The results show that oxidative stress caused by light is dependent on functional mitochondria and that the molecular mechanisms of apoptosis caused by hydrogen peroxide or light are similar but not identical. |
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Authors:
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Guang-Yu Li; Neville N Osborne |
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Publication Detail:
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Type: Journal Article Date: 2007-11-04 |
Journal Detail:
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Title: Brain research Volume: 1188 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 2008 Jan |
Date Detail:
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Created Date: 2007-12-24 Completed Date: 2008-06-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 35-43 Citation Subset: IM |
Affiliation:
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Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects, physiology*, radiation effects Apoptosis Inducing Factor / metabolism* Caspases / antagonists & inhibitors, metabolism Cell Compartmentation / drug effects, physiology, radiation effects Cell Line, Transformed Cell Survival / drug effects, physiology, radiation effects Cobalt / pharmacology Dose-Response Relationship, Drug Energy Metabolism / drug effects, physiology, radiation effects Enzyme Inhibitors / pharmacology Hydrogen Peroxide / pharmacology Light / adverse effects Mitochondria / drug effects, metabolism, radiation effects Oxidants / pharmacology Oxidative Stress / drug effects, physiology*, radiation effects Poly(ADP-ribose) Polymerases / antagonists & inhibitors, metabolism* Rats Retinal Diseases / metabolism*, physiopathology Retinal Ganglion Cells / drug effects, metabolism*, radiation effects Uncoupling Agents / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Inducing Factor; 0/Enzyme Inhibitors; 0/Oxidants; 0/Pdcd8 protein, rat; 0/Uncoupling Agents; 7440-48-4/Cobalt; 7722-84-1/Hydrogen Peroxide; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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