Hypersensitivity of ataxia-telangiectasia fibroblasts to a nitric oxide donor
| Autor: | Jillian E. Lowe, Susan A. Harcourt, Colin F. Arlett, Adam J Marcovitch, Michael H.L. Green, Irene C. Green |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Ataxia
Cell Drug Evaluation Preclinical Nitric Oxide Biochemistry Nitric oxide Drug Hypersensitivity S-Nitrosoglutathione Ataxia Telangiectasia chemistry.chemical_compound Reference Values Physiology (medical) medicine Humans Phosphatidylinositol Cell Death Neurodegeneration Fibroblasts medicine.disease Glutathione Molecular biology medicine.anatomical_structure Cell killing chemistry Ataxia-telangiectasia medicine.symptom Nitroso Compounds |
| Zdroj: | Free Radical Biology and Medicine. 22:343-347 |
| ISSN: | 0891-5849 |
| Popis: | Ataxia-telangiectasia (A-T) is a human autosomal recessive disease characterised by immunodeficiency, extreme sensitivity to ionising radiation and progressive cerebellar ataxia. The defective gene has recently been cloned and is a member of the phosphatidylinositol 3-kinase family. We have investigated the possibility that the neurodegeneration in A-T might be induced by an endogenously formed mutagen causing radiation-like damage. Nitric oxide is known to be formed in the cerebellum and we present evidence that A-T fibroblasts are hypersensitive to killing by the nitric oxide donor S-nitrosoglutathione (GSNO), as are fibroblasts from a radiosensitive individual without ataxia. Killing was determined as loss of colony forming ability. GSNO induces dose-dependent DNA strand breakage, but to no greater extent in A-T fibroblasts. Breakdown of GSNO to nitrite and nitrate appears to occur to the same extent in both normal and A-T fibroblasts. Cell killing by GSNO appears to be associated in both types of cell with formation of nitrite, rather than nitrate, as the ultimate oxidation product of nitric oxide. Copyright © 1996 Elsevier Science Inc. |
| Databáze: | OpenAIRE |
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