Involvement of Cytochrome P450 in Reactive Oxygen Species Formation and Cancer

Hrycay, Eugene G.; Bandiera, Stelvio M.

doi:10.1016/bs.apha.2015.03.003

Cited by 169 publications

(108 citation statements)

References 200 publications

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“…We hypothesized that the high level of ROS that we observed in the LEW rat peritoneal cells played a role in resistance to T. gondii infection. Mammalian phagocytic cells are known to produce large amounts of superoxide anion, which is a precursor for other highly reactive ROS such as hydrogen peroxide, hydroxyl radicals, and peroxynitrite (15). Therefore, to investigate whether superoxide anion was playing a role in the LEW rat's refractoriness to T. gondii, we infected LEW and BN rat peritoneal cells in the presence or absence of various concentrations of Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) (a superoxide scavenger) at a multiplicity of infection (MOI) of 1:4 (lower than the MOI used for the assay for Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The Cybrd1 gene is a member of the cytochrome b 561 gene family that encodes an iron-regulated protein (21). It can catalyze the reduction of ferric iron to form ferrous iron, which reacts with hydrogen peroxide to produce a hydroxyl radical via the Fenton reaction (15). In the normal physiological state, cellular ROS are detoxified by cellular antioxidant enzymes to prevent the development of oxidative stress, which is deleterious to cells (22,23).…”

Section: Discussionmentioning

confidence: 99%

“…the uninfected and infected LEW rat peritoneal cells contained higher levels of ROS than the BN rat peritoneal cells. Cyp2d3 and Cyp2d5 are cytochrome P450 family proteins that catalyze the microsomal and mitochondrial electron transport chains leading to the generation of ROS (including superoxide radical anion, hydroxyl radical, and hydrogen peroxide) in mammalian cells (15). The Cybrd1 gene is a member of the cytochrome b 561 gene family that encodes an iron-regulated protein (21).…”

Section: Discussionmentioning

confidence: 99%

“…Cytochrome P450 (CYP) enzymes catalyze the endogenous oxygenation of organic substrates through the reduction of molecular oxygen in mammalian CYPdependent microsomal and mitochondrial electron transport chains (13)(14)(15). During these enzymatic reactions, ROS are generated if the transfer of oxygen to a substrate is not tightly controlled (16).…”

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Inherent Oxidative Stress in the Lewis Rat Is Associated with Resistance to Toxoplasmosis

2017

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The course of Toxoplasma gondii infection in rats closely resembles that in humans. However, compared to the Brown Norway (BN) rat, the Lewis (LEW) rat is extremely resistant to T. gondii infection. Thus, we performed RNA sequencing analysis of the LEW rat versus the BN rat, with or without T. gondii infection, in order to unravel molecular factors directing robust and rapid early T. gondii-killing mechanisms in the LEW rat. We found that compared to the uninfected BN rat, the uninfected LEW rat has inherently higher transcript levels of cytochrome enzymes (Cyp2d3, Cyp2d5, and Cybrd1, which catalyze generation of reactive oxygen species [ROS]), with concomitant higher levels of ROS. Interestingly, despite having higher levels of ROS, the LEW rat had lower transcript levels for antioxidant enzymes (lactoperoxidase, microsomal glutathione S-transferase 2 and 3, glutathione S-transferase peroxidase kappa 1, and glutathione peroxidase) than the BN rat, suggesting that the LEW rat maintains cellular oxidative stress that it tolerates. Corroboratively, we found that scavenging of superoxide anion by Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) decreased the refractoriness of LEW rat peritoneal cells to T. gondii infection, resulting in proliferation of parasites in LEW rat peritoneal cells which, in turn, led to augmented cell death in the infected cells. Together, our results indicate that the LEW rat maintains inherent cellular oxidative stress that contributes to resistance to invading T. gondii, and they thus unveil new avenues for developing therapeutic agents targeting induction of host cell oxidative stress as a mechanism for killing T. gondii.KEYWORDS Brown Norway rat, cytochrome enzymes, Lewis rat, Toxoplasma gondii resistance, innate immunity, oxidative stress T oxoplasma gondii is a remarkably successful protozoan capable of infecting virtually all mammalian species, with about one-third of the world human population estimated to be infected. T. gondii infection and clinical outcome vary among species (1), depending on, among others, the immune status and genetic predisposition of the host (2-4). Unlike mice, rats are known to resist the development of clinical toxoplasmosis upon infection with T. gondii (5, 6). The phenomenon of T. gondii infection in rats closely mirrors the clinical progression of the infection in immunocompetent humans (7,8). This resemblance in the progression of toxoplasmosis between rats and humans warrants the use of rats as quintessential animal models for elucidating T. gondii infection in humans (7,8).Among rat strains, variations in resistance/susceptibility to toxoplasmosis have been reported. For instance, compared to the Brown Norway (BN) rat, the Lewis (LEW) rat is extremely resistant to T. gondii infection (9). This refractoriness of the LEW rat to toxoplasmosis has been associated with a rat genomic locus named Toxo1 on chromosome 10 (10). Pursuant to this, two genes called NLRP1 and ALOX1 in the orthologous Toxo1 locus on chromosome 17 in the human genome...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Inherent Oxidative Stress in the Lewis Rat Is Associated with Resistance to Toxoplasmosis

2017

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“…Sixth, exposure to toxicants activates cytochrome P450 monooxygenase (CYP450) in phase I xenobiotic biotransformation. Many reactive metabolites are unavoidably formed to cause oxidative damage [62].…”

Section: Oxidative Stressmentioning

confidence: 99%

Oxidative Stress in Urolithiasis

Boonla¹

2018

Reactive Oxygen Species (ROS) in Living Cells

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Oxygen is absolutely essential for the survival of our life. However, metabolic consumption of oxygen inevitably yields reactive oxygen species (ROS). Imbalance of ROS production and antioxidant capacity causes oxidative stress that potentially damages biomolecules leading to cell injury and death. In fact, ROS have two-faceted functions. Under physiologic condition, ROS function as signaling molecules and participate in maintaining redox balance. In pathology, ROS induce oxidative stress that critically involves in the development of several diseases including urolithiasis (UL). UL or urinary stone disease is a common urologic condition in all countries with progressively increasing prevalence. Most of UL are multifactorial with polygenic susceptibility and highly recurrent nature. Formation of urinary stones is driven by supersaturation of urinary lithogenic ions, and calcium oxalate (CaOx) is the most prevalent stone type. Oxidative stress clearly plays an active role in UL development. In vitro, lithogenic crystals induce ROS generation in renal tubular cells leading to oxidative stress, cell injury and release of inflammatory mediators. In nephrolithic rats, oxidative stress and CaOx deposit are gradually increased in the rats' kidneys. Intervention with antioxidants efficiently reduces oxidative damage and crystal deposits. Human studies show that patients with UL have increased oxidative stress and renal tubular injury relative to the non-stone-forming individuals. Increased oxidative lesions and inflammation are observed in the stone-containing kidneys of the patients. Furthermore, renal fibrosis mediated through tubular epithelial-mesenchymal transition is observed in kidneys of stone patients. Increased renal fibrosis is significantly associated with decreased kidney function. From therapeutic point of view, nutraceutical regimens that are able to reduce oxidative stress may be clinically useful alternatives for preventing stone formation and recurrence. This chapter has an intention to provide a basic knowledge of ROS generation and oxidative stress and up-to-date research findings of oxidative stress in UL based on the published articles as well as the author's studies.

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Tracking Metal Ions in Biology UsingX‐Ray Methods

James

Ent

Harris

2019

Encyclopedia of Inorganic and Bioinorganic Chemistry

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In this article, we describe the current state‐of‐play and potential future developments for a set of experimental methods that rely on X‐rays to probe metal ions in biological systems, especially X‐ray fluorescence imaging (XFI) and X‐ray absorption spectroscopy (XAS), which are almost always performed at synchrotron light sources to give suitable sensitivity to biologically realistic concentrations of metal ions. We do not take a comprehensive viewpoint, but rather choose particular applications to illustrate where these methods shine, directly probing the native coordination environment where no other techniques can, providing a complementary picture to that provided by other methods, and acting as a vital sanity check on results derived from other less direct methods.

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Involvement of Cytochrome P450 in Reactive Oxygen Species Formation and Cancer

Cited by 169 publications

References 200 publications

Inherent Oxidative Stress in the Lewis Rat Is Associated with Resistance to Toxoplasmosis

Inherent Oxidative Stress in the Lewis Rat Is Associated with Resistance to Toxoplasmosis

Oxidative Stress in Urolithiasis

Tracking Metal Ions in Biology UsingX‐Ray Methods

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