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Oltipraz-induced phase 2 enzyme response conserved in cells lacking mitochondrial DNA
Yee Liu Chua1, Dawei Zhang, Urs Boelsterli
1Department of Biochemistry, National University of Singapore, Singapore 117597, Singapore.
Biochemical and Biophysical Research Communications
|September 29, 2005
Summary
Oltipraz enhances the phase 2 enzyme response, boosting glutathione levels and protecting cells from oxidative stress. This protective mechanism remains effective even in cells lacking mitochondrial DNA (mtDNA).
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Oltipraz is a 1,2-dithiolethione known for inducing phase 2 enzymes, suggesting potential in cancer chemoprevention.
- Phase 2 enzymes are crucial for cellular defense against oxidative stress and xenobiotic metabolism.
- Mitochondria play a key role in cellular oxidative stress, making their function in response to chemopreventive agents an important area of study.
Purpose of the Study:
- To investigate the effect of oltipraz on the phase 2 enzyme response in lymphoblastic leukemia cells.
- To determine if oltipraz-induced protection against oxidative stress is dependent on mitochondrial DNA (mtDNA).
- To assess the impact of oltipraz on glutathione (GSH) levels and glutathione S-transferase (GST) activity in both parental and rho0 cells.
Main Methods:
- Treatment of parental (rho+) and mitochondrial DNA-deficient (rho0) CEM lymphoblastic leukemia cells with oltipraz.
- Measurement of total and mitochondrial glutathione (GSH) levels.
- Assay of glutathione S-transferase (GST) activity.
- Evaluation of cellular resistance to diethylmaleate-induced mitochondrial oxidation, membrane potential loss, and cell death.
Main Results:
- Oltipraz significantly increased both total and mitochondrial GSH levels and GST activity in both rho+ and rho0 cells.
- Both cell lines exhibited resistance to mitochondrial oxidation, loss of mitochondrial membrane potential, and cell death when challenged with diethylmaleate after oltipraz pretreatment.
- The phase 2 enzyme response, mediated by GSH-dependent systems, effectively blocked endogenous oxidative stress and cell death.
Conclusions:
- The phase 2 enzyme response induced by oltipraz enhances cellular defense mechanisms against oxidative stress.
- This protective response is functional and intact in lymphoblastic leukemia cells even in the absence of mitochondrial DNA (mtDNA).
- Oltipraz demonstrates potential as a chemopreventive agent by bolstering endogenous protective systems, independent of mtDNA integrity.
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