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Menadione effect on l-cysteine desulfuration in U373 cells
Maria Wróbel1, Halina Jurkowska
1Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland. mbwrobel@cyf-kr.edu.pl
Acta Biochimica Polonica
|May 24, 2007
Summary
Menadione exposure at non-cytotoxic levels reduces key enzyme activity and sulfane sulfur levels in U373 cells. This suggests menadione-induced reactive oxygen species contribute to oxidative stress by inhibiting sulfur metabolism.
Area of Science:
- Biochemistry
- Cell Biology
- Toxicology
Background:
- Menadione (2-methyl-1,4-naphthoquinone) is a compound known to induce oxidative stress.
- Sulfur-metabolizing enzymes like rhodanese and 3-mercaptopyruvate sulfurtransferase play crucial roles in cellular defense.
- Glutathione and sulfane sulfur are key indicators of cellular redox state.
Purpose of the Study:
- To investigate the impact of non-cytotoxic menadione concentrations on cellular sulfur metabolism.
- To determine the effect of menadione on the activity of rhodanese and 3-mercaptopyruvate sulfurtransferase.
- To assess the relationship between menadione exposure, reactive oxygen species, and oxidative stress markers.
Main Methods:
- U373 cells were incubated with 20 microM menadione for 1 hour.
- Enzyme activities of rhodanese and 3-mercaptopyruvate sulfurtransferase were measured.
- Levels of sulfane sulfur and glutathione were quantified.
- Reactive oxygen species generation was inferred.
Main Results:
- Menadione treatment significantly decreased rhodanese activity by 33% and 3-mercaptopyruvate sulfurtransferase activity by 20%.
- Sulfane sulfur levels dropped by approximately 23%, and glutathione levels decreased by 12%.
- Oxidation of sulfhydryl groups in enzyme active centers by menadione-generated reactive oxygen species was implicated.
Conclusions:
- Non-cytotoxic menadione concentrations impair critical sulfur-metabolizing enzymes in U373 cells.
- Reduced sulfane sulfur levels correlate with menadione-induced oxidative stress.
- Menadione's effects highlight its potential to disrupt cellular redox balance through enzyme inhibition.
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