Effects of Mannich bases on cellular glutathione and related enzymes of Jurkat cells in culture conditions.
Jurkat cells were exposed to representative acetophenone-derived mono Mannich bases 2 and 3 and also cyclic Mannich base C1 in culture conditions to see the alterations in the most abundant cellular thiol, glutathione and also some of the enzymes in its metabolic pathway. Jurkat cells were exposed to the compounds for 24 h in cell culture medium with fetal bovine serum (1%) at 37 degrees C under a humidified atmosphere of 95% air and 5% CO2. Mannich bases generally increased total glutathione level (123-151% of control). Glutathione S-transferase (GST) activity also increased (150-363% of control), while glutathione disulfide reductase (GRD) activity was not affected. The increase in cellular glutathione level may possibly result from de novo glutathione synthesis. The consumption of the glutathione due to alkylation by Mannich bases might have stimulated the enzymes in the gamma-glutamyl cycle in our experimental design, where the cells had nutrients and time to react with their feedback mechanisms. A remarkable increase in GST activity might be a compensatory up-regulation to detoxify Mannich bases by conjugating them with cellular thiols.
Gul
M
M
Department of Physiology, Faculty of Medicine, University of Kuopio, Finland.
Gul
H I
HI
Hänninen
O
O
D000098:Acetophenones / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D008352:Mannich Bases / Q000737:chemistry / Q000633:toxicity*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D013880:Thioredoxin-Disulfide Reductase
D000098:Acetophenones; D008352:Mannich Bases; D009247:NADH, NADPH Oxidoreductases; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase; C424443:Txnrd3 protein, mouse; D005982:Glutathione Transferase; D005978:Glutathione; C038699:acetophenone