Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

Kim, Sangsoo Daniel; Antenos, Monica; Squires, E. J.; Kirby, Gordon M.

doi:10.1016/j.taap.2013.04.013

Cited by 19 publications

(22 citation statements)

References 174 publications

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“…First, the number of studied subjects in the current study was relatively small, and CTLs were not well matched regarding age, sex, and BMI. Second, it has been suggested that cytochrome P450 2A5 (CYP2A5) plays a key role in bilirubin clearance [30]; however, P450 2A5 genotypes and their activity were not considered in this study. Third, we did not determine the total antioxidant capacity of bilirubin and albumin in anti-NMDAR encephalitis.…”

Section: Discussionmentioning

confidence: 99%

Serum Bilirubin and Albumin in Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Shu

Chen

et al. 2018

Neuroimmunomodulation

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Background and Objective: Low serum levels of bilirubin and albumin are associated with multiple autoimmune diseases, but their role in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is unknown. Methods: Serum bilirubin and albumin levels were evaluated in 60 patients with anti-NMDAR encephalitis, 50 cryptococcal encephalitis, and 145 healthy controls (CTLs). Of the 60 anti-NMDAR encephalitis patients, 30 had a follow-up evaluation at 3 months after admission. Results: Serum bilirubin and albumin levels were both significantly lower in anti-NMDAR encephalitis than in CTLs, and serum bilirubin levels were significantly lower in anti-NMDAR encephalitis than in cryptococcal encephalitis. Serum bilirubin levels were significantly lower in patients with psychiatric symptoms, with severe impairment, and with limited responses to treatment than those without psychiatric symptoms, with mild impairment, and with favorable responses to treatment, respectively. A follow-up evaluation of 30 patients revealed that the modified Rankin Scale scores were significantly decreased after treatment. Serum bilirubin significantly associated with serum albumin, and plasma hemoglobin. Conclusions: Our results revealed for the first time an association between the serum levels of bilirubin in the anti-NMDAR encephalitis. Further studies investigating the role of bilirubin and albumin in anti-NMDAR encephalitis are required.

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Section: Discussionmentioning

confidence: 99%

Serum Bilirubin and Albumin in Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Shu

Chen

et al. 2018

Neuroimmunomodulation

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“…Bilirubin, the primary form (unconjugated form) of bilirubin circulating in healthy individuals, has antioxidant properties [109]. Recent studies report bilirubin treatment can increase the nuclear accumulation of NRF2 proteins and activation of NRF2 which will up-regulate heme-oxygenase-1 (HO-1) expression in HepG2 cells and primary mouse hepatocytes [110]. Melatonin is a tryptophan metabolite.…”

Section: Non-enzymatic Antioxidantsmentioning

confidence: 99%

Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species

Farrar

et al. 2017

Cell Physiol Biochem

1,279

689

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Reactive oxygen species (ROS) are produced by living cells as normal cellular metabolic byproduct. Under excessive stress conditions, cells will produce numerous ROS, and the living organisms eventually evolve series of response mechanisms to adapt to the ROS exposure as well as utilize it as the signaling molecules. ROS molecules would trigger oxidative stress in a feedback mechanism involving many biological processes, such as apoptosis, necrosis and autophagy. Growing evidences have suggested that ROS play a critical role as the signaling molecules throughout the entire cell death pathway. Overwhelming production of ROS can destroy organelles structure and bio-molecules, which lead to inflammatory response that is a known underpinning mechanism for the development of diabetes and cancer. Cytochrome P450 enzymes (CYP) are regarded as the markers of oxidative stress, can transform toxic metabolites into ROS, such as superoxide anion, hydrogen peroxide and hydroxyl radical which might cause injury of cells. Accordingly, cells have evolved a balanced system to neutralize the extra ROS, namely antioxidant systems that consist of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidases (GPxs), thioredoxin (Trx) as well as the non-enzymatic antioxidants which collectively reduce oxidative state. Herein, we review the recent novel findings of cellular processes induced by ROS, and summarize the roles of cellular endogenous antioxidant systems as well as natural anti-oxidative compounds in several human diseases caused by ROS in order to illustrate the vital role of antioxidants in prevention against oxidative stress.

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“…Recent findings have shown that in mice, CYP2A5 mRNA expression is upregulated following exposure to various chemical hepatotoxins and during pathophysiological conditions (e.g. by altered lipid status and energy homeostasis or elevated levels of bilirubin) in which the levels of most CYPs are either unchanged or downregulated [13,14]. The genes of the mouse CYP2A5 and human ortholog CYP2A6 are regulated in a complex and exceptional way where the promoter genes interact with multiple transcription factors activated by stress like hnRNP A1, Nrf2, HNF4α or AhR (heterologous nuclear ribonucleoprotein A1, nuclear factor-E2 p45-regulated factor 2, hepatocyte nuclear factor 4α, aryl hydrocarbon receptor) [1].…”

Section: Discussionmentioning

confidence: 99%

Altered cytochrome P450 activities and expression levels in the liver and intestines of the monosodium glutamate-induced mouse model of human obesity

et al. 2015

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Cytochrome P450 2A5 and bilirubin: Mechanisms of gene regulation and cytoprotection

Cited by 19 publications

References 174 publications

Serum Bilirubin and Albumin in Anti-<b><i>N</i></b>-Methyl-D-Aspartate Receptor Encephalitis

Serum Bilirubin and Albumin in Anti-<b><i>N</i></b>-Methyl-D-Aspartate Receptor Encephalitis

Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species

Altered cytochrome P450 activities and expression levels in the liver and intestines of the monosodium glutamate-induced mouse model of human obesity

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