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Oxidative protein damage causes chromium toxicity in yeast
Edward R Sumner1, Anupama Shanmuganathan2, Theodora C Sideri1
1School of Biology, Institute of Genetics, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Microbiology (Reading, England)
|June 9, 2005
Summary
Chromium (Cr) toxicity in yeast is primarily caused by oxidative damage to proteins. This study shows that peptide methionine sulfoxide reductase (MSR) enzymes are crucial for Cr resistance, highlighting protein oxidation as a key mechanism.
Area of Science:
- Microbiology
- Environmental Toxicology
- Biochemistry
Background:
- Chromium (Cr) is a toxic metal, and its oxidative damage to microbial cells is known.
- The precise role of oxidation in Cr toxicity has remained uncertain.
- Understanding Cr toxicity mechanisms is vital for environmental and health risk assessment.
Purpose of the Study:
- To elucidate the oxidative mechanism of chromium (Cr) toxicity in Saccharomyces cerevisiae.
- To identify the specific macromolecular targets of Cr-induced oxidative damage.
- To investigate the role of antioxidant enzymes in cellular resistance to Cr.
Main Methods:
- Utilized Saccharomyces cerevisiae mutants deficient in superoxide dismutase (sod1Δ), glutathione peroxidases (gpx), DNA repair enzymes (ogg1Δ, rad30Δ), and peptide methionine sulfoxide reductases (msrAΔ, msrBΔ).
- Assessed Cr(VI) sensitivity under aerobic and anaerobic conditions.
- Measured cellular protein carbonyl levels as an indicator of protein oxidation.
- Investigated the effect of overexpressing MSR enzymes on Cr resistance.
Main Results:
- A sod1Δ mutant showed hypersensitivity to Cr(VI) under aerobic conditions, suppressed anaerobically, indicating a role for superoxide dismutase activity.
- Mutants defective in phospholipid hydroperoxide reduction or DNA oxidation repair were not Cr-sensitive.
- Peptide methionine sulfoxide reductase (MSR) mutants (msrAΔ, msrBΔ) exhibited Cr sensitivity, while MSR overexpression conferred Cr resistance.
- Cr exposure rapidly increased cellular protein carbonylation by approximately 20-fold, with specific targeting of glycolytic enzymes and heat-shock proteins.
Conclusions:
- Oxidative damage to cellular proteins is a primary mechanism underlying chromium (Cr) toxicity in Saccharomyces cerevisiae.
- Peptide methionine sulfoxide reductases (MSRs) play a critical role in protecting cells against Cr-induced protein oxidation and toxicity.
- This study establishes an oxidative mode of Cr toxicity, specifically targeting proteins, rather than DNA or lipids.