| Mechanisms of N-acetylcysteine-driven enhancement of MK886-induced apoptosis. | |
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MedLine Citation:
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PMID: 16817014 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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N-Acetylcysteine (NAC), besides being a precursor of glutathione, has an array of other effects including an ability to scavenge free radicals, modulate gene expression and signal transduction pathways, and regulate cell survival and apoptosis. At concentrations lower than 20 mmol/L, NAC is nontoxic to cultured cells and can protect against apoptosis induced by a number of agents. A few recent reports, however, have indicated that NAC can also increase apoptosis. MK886, a 5-lipoxygenase activating protein (FLAP) inhibitor, induces apoptosis in many cell lines by an unknown mechanism that is independent of FLAP and lipoxygenase activity but is possibly related to effects on kinases such as Akt. In Jurkat T lymphocytes, NAC pretreatment (10 mmol/L) enhanced MK886-induced apoptosis by 2.4-fold. Following NAC-MK886 treatment, there was a significant increase in caspase-3 activity, and a decrease in mitochondrial transmembrane potential compared to MK886 alone. However, the extent of cytochrome c release was comparable between MK886 alone and MK886-NAC treatments. The enhancement of MK886-induced apoptosis by 10 mmol/L NAC appears to be partly related to a decrease in pH caused by this concentration of NAC, because an acidic environment favors activation of effector caspases and triggering of mitochondrial apoptosis. However, because neutralized NAC also enhanced apoptosis (1.6-fold), a direct role for NAC in augmenting the apoptotic pathways initiated by MK886 is suggested. |
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Authors:
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V S Deshpande; James P Kehrer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-06-30 |
Journal Detail:
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Title: Cell biology and toxicology Volume: 22 ISSN: 0742-2091 ISO Abbreviation: Cell Biol. Toxicol. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-07-12 Completed Date: 2007-02-27 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 8506639 Medline TA: Cell Biol Toxicol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 303-11 Citation Subset: IM |
Affiliation:
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Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, USA. vaidehee@hotmail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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pharmacology* Annexin A5 / pharmacology Apoptosis* Carrier Proteins / metabolism Caspase 3 / metabolism Cytochromes c / metabolism Dose-Response Relationship, Drug Enzyme Activation Fluorescein-5-isothiocyanate / pharmacology Free Radical Scavengers / pharmacology Humans Hydrogen-Ion Concentration Indoles / pharmacology* Jurkat Cells Membrane Proteins / metabolism Propidium / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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CA83701/CA/NCI NIH HHS; ES07784/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/5-lipoxygenase-activating protein; 0/Annexin A5; 0/Carrier Proteins; 0/Free Radical Scavengers; 0/Indoles; 0/Membrane Proteins; 118414-82-7/L 663536; 3326-32-7/Fluorescein-5-isothiocyanate; 36015-30-2/Propidium; 616-91-1/Acetylcysteine; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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