Molecular role of cytochrome P4501A enzymes in oxidative stress

Stading, Rachel; Chang, Chun Ming; Couroucli, Xanthi I.; Lingappan, Krithika; Moorthy, Bhagavatula

doi:10.1016/j.cotox.2020.07.001

Cited by 44 publications

(24 citation statements)

References 53 publications

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“…Our recent study [19] showing the increased susceptibility to hyperoxic lung injury of mice lacking the gene for nrf2, and the rescue of this phenotype by the CYP1A1 inducer β-napthoflavone, lends further credence to the hypothesis that both Nrf2regulated enzymes (e.g., NQ01) and CYP1A enzymes play a beneficial role in oxygen injury. While CYP1A1 might protect the cells from oxidative stress by metabolizing toxic lipid hydroperoxides [16][17][18][19][20], it is possible that NQO1 in the current study might have protected cells from oxidative stress by metabolizing quinones and semiquniones [21,22]. The innovative aspect of our current study is that our results show a decrease in the extent of induction of CYP1A1 by hyperoxia in NQO1-NQO1 cells, suggesting a role for NQO1 in the regulation of CYP1A1 expression.…”

mentioning

confidence: 51%

“…ROS generated in hyperoxic conditions lead to profound cell damage through direct DNA damage, lipid peroxidation, protein oxidation, and alteration of transcription factors [4,12]. Recent studies from our laboratory have shown a protective effect of cytochrome P450 (CYP) 1A enzymes against hyperoxic lung injury in vivo [13][14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

“…Oxidative Medicine and Cellular Longevity [13][14][15][16][17][18][19]42] have clearly shown the role of both CYP1A1 and NQO1 in the protection against oxidative injury. Our recent study [19] showing the increased susceptibility to hyperoxic lung injury of mice lacking the gene for nrf2, and the rescue of this phenotype by the CYP1A1 inducer β-napthoflavone, lends further credence to the hypothesis that both Nrf2regulated enzymes (e.g., NQ01) and CYP1A enzymes play a beneficial role in oxygen injury.…”

mentioning

confidence: 99%

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Role of Human NADPH Quinone Oxidoreductase (NQO1) in Oxygen‐Mediated Cellular Injury and Oxidative DNA Damage in Human Pulmonary Cells

Burke

Cai

Zhou

et al. 2021

Oxidative Medicine and Cellular Longevity

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Supplemental oxygen administration is frequently used in premature infants and adults with pulmonary insufficiency. NADPH quinone oxidoreductase (NQO1) protects cells from oxidative injury by decreasing reactive oxygen species (ROS). In this investigation, we tested the hypothesis that overexpression of NQO1 in BEAS-2B cells will mitigate cell injury and oxidative DNA damage caused by hyperoxia and that A-1221C single nucleotide polymorphism (SNP) in the NQO1 promoter would display altered susceptibility to hyperoxia-mediated toxicity. Using stable transfected BEAS-2B cells, we demonstrated that hyperoxia decreased cell viability in control cells (Ctr), but this effect was differentially mitigated in cells overexpressing NQO1 under the regulation of the CMV viral promoter, the wild-type NQO1 promoter (NQO1-NQO1), or the NQO1 promoter carrying the SNP. Interestingly, hyperoxia decreased the formation of bulky oxidative DNA adducts or 8-hydroxy-2 ′ -deoxyguanosine (8-OHdG) in Ctr cells. qPCR studies showed that mRNA levels of CYP1A1 and NQO1 were inversely related to DNA adduct formation, suggesting the protective role of these enzymes against oxidative DNA injury. In SiRNA experiments entailing the NQO1-NQO1 promoter, hyperoxia caused decreased cell viability, and this effect was potentiated in cells treated with CYP1A1 siRNA. We also found that hyperoxia caused a marked induction of DNA repair genes DDB2 and XPC in Ctr cells, supporting the idea that hyperoxia in part caused attenuation of bulky oxidative DNA lesions by enhancing nucleotide excision repair (NER) pathways. In summary, our data support a protective role for human NQO1 against oxygen-mediated toxicity and oxidative DNA lesions in human pulmonary cells, and protection against toxicity was partially lost in SNP cells. Moreover, we also demonstrate a novel protective role for CYP1A1 in the attenuation of oxidative cells and DNA injury. Future studies on the mechanisms of attenuation of oxidative injury by NQO1 should help in developing novel approaches for the prevention/treatment of ARDS in humans.

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confidence: 51%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Role of Human NADPH Quinone Oxidoreductase (NQO1) in Oxygen‐Mediated Cellular Injury and Oxidative DNA Damage in Human Pulmonary Cells

Burke

Cai

Zhou

et al. 2021

Oxidative Medicine and Cellular Longevity

Self Cite

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“…CYP1A are a family of monooxygenase enzymes involved in biotransformation reactions ( Danielson, 2002 ). Presence of CYP1A1 polymorphic variants changes the gene expression and/ activity resulting in the altered redox balance ( Stading et al, 2020 ). This imbalance can cause chronic inflammation in the lungs aggravating the disease pathogenesis ( Hussain et al, 2014 ; Stading et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Human genetic factors associated with pneumonia risk, a cue for COVID-19 susceptibility

Guin

Yadav

Singh

et al. 2022

Infection, Genetics and Evolution

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“…Such immune response related genes may serve as good candidates in establishing a genetic association in infectious diseases. Therefore, we considered xenobiotic detoxification genes encoding, CYP enzymes, which are also involved in inflammatory responses by inducing oxidative stress on encountering foreign bodies[20]. This meta-analysis reiterates prior observations that suggest a genetic contribution of CYP1A1 to pneumonia risk, and provides a more precise estimate of the risk of individuals carrying CYP1A1 genetic variants (rs2606345, rs4646903, rs1048943) for developing pneumonia.…”

Section: Discussionmentioning

confidence: 99%

Human genetic factors associated with pneumonia susceptibility, a cue for COVID-19 mortality

Guin

Yadav

Singh

et al. 2021

Preprint

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The risk for community acquired pneumonia (CAP) is partially driven by genetics. To identify the CAP-associated genetic risk loci, we performed a meta-analysis of clinically diagnosed CAP (3310 individuals) with 2655 healthy controls. The findings revealed CYP1A1 variants (rs2606345, rs4646903, rs1048943) associated with pneumonia. We observed rs2606345 [G vs T; OR=1.49(1.29-1.69); p=0.0001; I2= 15.5%], and rs1048943 [T vs G; OR= 1.31(0.90-1.71); p=0.002; I2=19.3%] as risk markers and rs4646903 [T vs C; OR= 0.79(0.62-0.96); p=0.03; I2=0%] as a protective marker for susceptibility to CAP, when compared with healthy controls. Our meta-analysis showed the presence of CYP1A1 SNP alleles contributing significant risk toward pneumonia susceptibility. Interestingly, we observed a striking difference of allele frequency for rs2606345 (CYP1A1) among Europeans, Africans and Asians which may provide a possible link for observed variations in death due to coronavirus disease 2019 (COVID-19), a viral pneumonia. We report, for the first time, a significant positive correlation for the risk allele (T or A) of rs2606345, with a higher COVID-19 mortality rate worldwide and within a genetically heterogeneous nation like India. Mechanistically, the risk allele ′A′ (rs2606345) is associated with lower expression of CYP1A1 and presumably leads to reduced capacity for xenobiotic detoxification. We note that ambient air pollution, a powerful inducer of CYP1A1 gene expression, is globally associated with lower, not higher mortality, as would normally be predicted. In conclusion, we find that CYP1A1 alleles are associated with CAP mortality, presumably via altered xenobiotic metabolism. We speculate that gene-environment interactions governing CYP1A1 expression may influence COVID-19 mortality.

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Molecular role of cytochrome P4501A enzymes in oxidative stress

Cited by 44 publications

References 53 publications

Role of Human NADPH Quinone Oxidoreductase (NQO1) in Oxygen‐Mediated Cellular Injury and Oxidative DNA Damage in Human Pulmonary Cells

Role of Human NADPH Quinone Oxidoreductase (NQO1) in Oxygen‐Mediated Cellular Injury and Oxidative DNA Damage in Human Pulmonary Cells

Human genetic factors associated with pneumonia risk, a cue for COVID-19 susceptibility

Human genetic factors associated with pneumonia susceptibility, a cue for COVID-19 mortality

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