| Nitric oxide and BCNU chemoresistance in C6 glioma cells: role of S-nitrosoglutathione. | |
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MedLine Citation:
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PMID: 15110396 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inducible nitric oxide synthase (iNOS or NOS2) is expressed in malignant glioma. Previously we noted that C6 glioma cells overexpressing NOS2 displayed chemoresistance against 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and other chloroethylnitrosourea derivatives with carbamoylating action. Herein we report experimental evidence supporting the contention that this NOS2 effect is mediated, at least in part, by S-nitrosoglutathione (GSNO), a potent antioxidant derived from interaction of NO and glutathione. Out of three NO donors tested, only GSNO was effective in protecting glioma cells against BCNU cytotoxicity. Furthermore, the protective effect of GSNO, similar to that of NOS2, was confined to carbamoylating, but not alkylating action. Experimental manipulations that were expected to increase or decrease cellular GSNO stores, as confirmed by immunocytochemical staining using a GSNO-specific antibody and HPLC analysis of GSNO contents in culture medium, led respectively to enhanced or reduced chemoresistance against carbamoylating cytotoxicity. Finally, neocuproine, a selective cuprous ion chelator known to neutralize GSNO actions, abolished NOS2-mediated chemoresistance against carbamoylating agents. Our results reveal a novel action of NOS2/GSNO that may potentially contribute to the development of chemoresistance against BCNU, which remains a mainstay in chemotherapy for glioblastoma multiforme. |
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Authors:
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Ding-I Yang; Jiu-Haw Yin; Tzyh-Chwen Ju; Long-Shiuh Chen; Chung Y Hsu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Free radical biology & medicine Volume: 36 ISSN: 0891-5849 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2004 May |
Date Detail:
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Created Date: 2004-04-27 Completed Date: 2004-11-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 1317-28 Citation Subset: IM |
Affiliation:
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Institute of Neuroscience, Tzu Chi University, Hualien, Taiwan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alkylation Animals Antineoplastic Agents, Alkylating / toxicity* Antioxidants / therapeutic use* Carbamates / metabolism Carmustine / toxicity* Chelating Agents / pharmacology Drug Resistance, Neoplasm* Glioma / drug therapy*, metabolism, pathology Nitric Oxide / metabolism* Nitric Oxide Synthase / metabolism Nitric Oxide Synthase Type II Phenanthrolines / pharmacology Rats S-Nitrosoglutathione / therapeutic use* Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Alkylating; 0/Antioxidants; 0/Carbamates; 0/Chelating Agents; 0/Phenanthrolines; 10102-43-9/Nitric Oxide; 154-93-8/Carmustine; 484-11-7/neocuproine; 57564-91-7/S-Nitrosoglutathione; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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