| Activation of Cell Death Mediated by Apoptosis-Inducing Factor Due to the Absence of Poly(ADP-ribose) Glycohydrolase. | |
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MedLine Citation:
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PMID: 21366272 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We previously demonstrated that the absence of poly(ADP-ribose) glycohydrolase (PARG) led to increased cell death following DNA-damaging treatments. Here, we investigated cell death pathways following UV treatment. Decreased amounts of PARG-null embryonic trophoblast stem (TS) cells were observed following doses of 10-100 J/m2 as compared to wild-type. In wild-type cells, caspase-cleaved poly(ADP-ribose) polymerase-1 (PARP-1) and activated caspase-3 were detected at 12 to 24 h after UV treatment. Surprisingly, both were detected at decreased levels only after 24 h in PARG null-TS cells, indicating a decreased and delayed presence of caspase-mediated events. Further, a time and dose-dependent accumulation of poly(ADP-ribose) (PAR) levels after UV was observed in PARG null-TS cells and not in wild-type cells. Determination of the levels of nicotinamide adenine dinucleotide (NAD+), the substrate for PAR synthesis and a coenzyme in cellular redox reactions, demonstrated a UV dose-dependent decrease of NAD+ in wild-type cells, while NAD+ levels in PARG null-TS cells remained at higher levels. This indicates no depletion of NAD+ in PARG null-TS cells following increased levels of PAR. Lastly, cell death mediated by apoptosis-inducing factor (AIF) was analyzed due to its dependence on increased PAR levels. The results demonstrate nuclear AIF translocation only in PARG null-TS cells, which demonstrates the presence of AIF-mediated cell death. Taken together, we provide compelling evidence that the absence of PARG leads to decreased caspase-3 activity and the specific activation of AIF-mediated cell death. Therefore, the absence of PARG may provide a strategy to specifically induce an alternative apoptotic pathway. |
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Authors:
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Yiran Zhou; Xiaoxing Feng; David W Koh |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-2 |
Journal Detail:
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Title: Biochemistry Volume: - ISSN: 1520-4995 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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