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Benzo[a]pyrene increases the Nrf2 content by downregulating the Keap1 message
Phuong Minh Nguyen1, Miki Susanto Park, Marilynn Chow
1Department of Labour Physiology, Vietnam Military Medical University, Hadong, Hanoi, Vietnam.
Summary
Benzo[a]pyrene (BaP) downregulates Kelch-like ECH-associated protein 1 (Keap1) in Jurkat cells, increasing nuclear nuclear factor erythroid 2-related factor (Nrf2) protein. This occurs without reactive oxygen species involvement, impacting Nrf2 target gene expression.
Area of Science:
- Toxicology
- Molecular Biology
- Cell Biology
Background:
- Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon found in environmental pollutants.
- The Keap1-Nrf2 pathway is a critical regulator of cellular defense against oxidative stress.
- Understanding how environmental toxins modulate this pathway is crucial for assessing health risks.
Purpose of the Study:
- To investigate the effect of BaP on Keap1 and Nrf2 expression in Jurkat cells.
- To elucidate the mechanism by which BaP influences the Keap1-Nrf2 pathway.
- To compare the effects of BaP in Jurkat cells with those in Hepa1c1c7 cells.
Main Methods:
- Suppresss subtractive hybridization was used to identify differentially expressed transcripts.
- Quantitative real-time PCR and Western blotting were employed to measure mRNA and protein levels.
- Cell treatments included BaP and 3-(4-morpholinyl)propyl isothiocyanate.
Main Results:
- BaP significantly downregulated Keap1 mRNA and protein levels in Jurkat cells.
- Nuclear Nrf2 protein content increased by 2.6-fold in BaP-treated Jurkat cells.
- BaP also downregulated Keap1 in Hepa1c1c7 cells, but Jurkat cells showed distinct metabolic profiles.
Conclusions:
- BaP, independent of its metabolites and reactive oxygen species, upregulates nuclear Nrf2 by suppressing Keap1 expression in Jurkat cells.
- The findings highlight a novel mechanism of Nrf2 activation by BaP.
- This provides insights into the molecular mechanisms underlying BaP-induced cellular responses.
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