Effect of methotrexate (MTX) on NAD(P)+ dehydrogenases of HeLa cells: malic enzyme, 2-oxoglutarate and isocitrate dehydrogenases
| Autor: | Annibal P. Campello, Maria Benigna M. Oliveira, M. L. W. Kluppel, Nilce N. Caetano, Eva Gunilla Skare Carnieri |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
musculoskeletal diseases
biology Succinate dehydrogenase Clinical Biochemistry Malic enzyme Dehydrogenase Cell Biology General Medicine Mitochondrion biology.organism_classification Biochemistry Molecular biology HeLa Isocitrate dehydrogenase biology.protein Malic enzyme activity NAD+ kinase skin and connective tissue diseases |
| Zdroj: | Cell Biochemistry and Function. 15:259-264 |
| ISSN: | 1099-0844 0263-6484 |
| DOI: | 10.1002/(sici)1099-0844(199712)15:4<259::aid-cbf749>3.0.co;2-d |
| Popis: | The effects of methotrexate (MTX) on oxygen uptake by permeabilized HeLa cells were evaluated. MTX did not inhibit state III respiration when the oxidizable substrate was succinate, but when the substrates were 2-oxoglutarate or isocitrate the respiration decreased about 50 per cent at 1.0 mM concentration of the drug. This effect was explained by inhibition of 2-oxoglutarate and isocitrate dehydrogenases by MTX. No effect was observed on succinate dehydrogenase. An evaluation of the effects of MTX on malic enzyme activity as measured by pyruvate plus lactate production in intact cells supplied with malate showed a decrease of about 40 per cent in metabolite production using 0.4 mM MTX. HeLa cell malic enzyme, as observed for other tumour cells, is compartmentalized in mitochondria and cytosol, and is another example of a dehydrogenase inhibited by MTX. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text