Glyoxalase I in detoxification: studies using a glyoxalase I transfectant cell line
| العنوان: | Glyoxalase I in detoxification: studies using a glyoxalase I transfectant cell line |
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| المؤلفون: | Eileen S. Walsh, Kenneth D. Tew, Sulabha Ranganathan |
| المصدر: | Biochemical Journal. 309:127-131 |
| بيانات النشر: | Portland Press Ltd., 1995. |
| سنة النشر: | 1995 |
| مصطلحات موضوعية: | DNA, Complementary, Antineoplastic Agents, Transfection, Biochemistry, Mice, chemistry.chemical_compound, Lactoylglutathione lyase, Neoplasms, Animals, Humans, Cytotoxic T cell, Cytotoxicity, Molecular Biology, biology, Methylglyoxal, Lactoylglutathione Lyase, 3T3 Cells, Cell Biology, Glutathione, Pyruvaldehyde, chemistry, Cell culture, Inactivation, Metabolic, biology.protein, Research Article, Glyoxalase system |
| الوصف: | The glyoxalase system (glyoxalase I, glyoxalase II and GSH as cofactor) is involved in the detoxification of methylglyoxal (a byproduct of the glycolytic pathway) and other alpha-oxoaldehydes. We have transfected a 622 bp cDNA encoding human glyoxalase I into murine NIH3T3 cells. The recipient cells were shown to express elevated transcript and protein levels and a 10-fold increase in glyoxalase I enzyme activity. This was accompanied by an increased tolerance for exogenous methylglyoxal and enhanced resistance to the cytotoxic effects of two glyoxalase I inhibitors (s-p-bromobenzylglutathione diethyl ester and s-p-bromobenzylglutathione dicyclopentyl ester), a glutathione analogue [gamma-glutamyl-(S)-(benzyl)cysteinyl-(R)-(-)-phenylglycine diethyl ester] and the anti-cancer drugs mitomycin C and adriamycin. Steady-state levels of GSH were significantly lower in the transfected cells, perhaps reflecting increased flux as a consequence of elevated glyoxalase activity. This decrease did not alter the sensitivity to the alkylating agent chlorambucil. Although transfection did not affect the growth or doubling time of the NIH3T3 cells, analysis of glyoxalase I activity showed a consistent increase in tumour tissue when compared with pair-matched controls. Thus increased glyoxalase I is associated with the malignant phenotype and may also contribute to protection against the cytotoxicity of certain anti-cancer drugs. |
| تدمد: | 1470-8728 0264-6021 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a93ab615bbe685c7cfd725a0f70d704Test https://doi.org/10.1042/bj3090127Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4a93ab615bbe685c7cfd725a0f70d704 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14708728 02646021 |
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