Additive Effects of Mitochondrion-targeted Cytochrome CYP2E1 and Alcohol Toxicity on Cytochrome c Oxidase Function and Stability of Respirosome Complexes

Bansal, Sandhya; Srinivasan, Satish; Sadagopan, Suresh Kumar Ananda; Chowdhury, Anindya Roy; Selvaraj, Venkatesh; Kalyanaraman, Balaraman; Joseph, Joy; Avadhani, Narayan G.

doi:10.1074/jbc.m111.314062

Cited by 28 publications

(28 citation statements)

References 79 publications

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“…A similar conclusion was reached by Robin's group recently using a different targeting approach (29). We also demonstrated that mitochondria-targeted CYP2E1 caused excessive and direct damage to mitochondrial cytochrome c oxidase (CcO), which was nearly completely reversed by the mitochondria-targeted antioxidants Mito-CP and Mito-Q (27,30), providing further confirmation that mitochondrial ROS in the presence of added alcohol is a key factor in inducing cellular toxicity.…”

supporting

confidence: 85%

“…In this new location, mitochondrial CYP2E1 interacts with and accepts electrons from the mitochondrial adrenodoxin (Adx) and adrenodoxin reductase (Adr) system and efficiently catalyzes the metabolism of an array of substrates. Using an in vitro mutagenesis approach, we showed that mitochondria-targeted CYP2E1 potentiated a higher level of alcohol-mediated ROS production and cell injury than the microsomal CYP2E1 in COS-7 and HEPG2 cells (27,28). A similar conclusion was reached by Robin's group recently using a different targeting approach (29).…”

supporting

confidence: 72%

“…The cells were harvested 48 h post-transfection, washed with phosphate-buffered saline (PBS), and used for isolating subcellular fractionations as described previously (27,28). The Met at position 22 was also mutated to Ala in the CYP2E1-DHFR fusion protein using the same strategy.…”

Section: Methodsmentioning

confidence: 99%

“…The modification involves the use of 5 g of brain cytosolic fraction as source of esterase for assaying mitochondrial fractions as described before (27,28). Stable non-fluorescent DCFH-DA (2.5 M in methanol) was used in 200 l of an assay mixture containing 135 l of PBS, 20 g of mitochondrial protein, 5 g of brain cytosol, and 0.1 mM NADPH.…”

Section: Measurement Of Ros Production Using 2ј7ј-dichlorodihydroflumentioning

confidence: 99%

“…Assay of Cytochrome c Oxidase Activity-CcO activity was measured by incubating 10 g of freeze-thawed mitochondrial extract prepared from control or alcohol-treated (100 mM for 48 h) cells, in 1 ml of assay medium (25 mM potassium phosphate, pH 7.4, containing 0.45 mM dodecyl maltoside and 15 M reduced cytochrome c) and measuring the decrease in absorbance at 550 nm due to cytochrome c oxidation (27,68). In some assays, cells were also treated with Mito-CP (2 M) or disulfiram (25 M) as indicated.…”

Section: Measurement Of Ros Production Using 2ј7ј-dichlorodihydroflumentioning

confidence: 99%

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Human Cytochrome P450 2E1 Mutations That Alter Mitochondrial Targeting Efficiency and Susceptibility to Ethanol-induced Toxicity in Cellular Models

Bansal

Anandatheerthavarada

Prabu

et al. 2013

Journal of Biological Chemistry

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Background: Induced expression of CYP2E1 is known to enhance alcohol liver toxicity. Results: Novel mutations W23R/W30R and L32N in human CYP2E1 alter mitochondrial and microsomal targeting efficiency. Conclusion: Human variants with altered targeting modulate susceptibility of cells to alcohol. Significance: Carriers of the novel W23R/W30R mutation in CYP2E1 are likely to be more susceptible to alcohol toxicity.

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supporting

confidence: 85%

supporting

confidence: 72%

Section: Methodsmentioning

confidence: 99%

Section: Measurement Of Ros Production Using 2ј7ј-dichlorodihydroflumentioning

confidence: 99%

Section: Measurement Of Ros Production Using 2ј7ј-dichlorodihydroflumentioning

confidence: 99%

See 3 more Smart Citations

Human Cytochrome P450 2E1 Mutations That Alter Mitochondrial Targeting Efficiency and Susceptibility to Ethanol-induced Toxicity in Cellular Models

Bansal

Anandatheerthavarada

Prabu

et al. 2013

Journal of Biological Chemistry

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Mitochondria‐Targeted Cytochromes P450 Modulate Adverse Drug Metabolism and Xenobiotic‐Induced Toxicity

Raza

Guengerich

Avadhani

2018

Mitochondrial Dysfunction Caused by Drugs and Environmental Toxicants

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Hepatoprotective Effects of a Proprietary Glycyrrhizin Product during Alcohol Consumption: A Randomized, Double‐Blind, Placebo‐Controlled, Crossover Study

Chigurupati¹,

Auddy²,

Biyani³

et al. 2016

Phytotherapy Research

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Traditionally, licorice has been used to treat liver problems. Glycyrrhizin, the primary active compound, has been shown to suppress elevations in liver enzymes that occur when the liver becomes diseased or damaged. This randomized, double-blind, placebo-controlled, crossover study evaluated the hepatoprotective effects of a proprietary glycyrrhizin product during alcohol consumption. Twelve healthy individuals (six male and six female subjects) in a clinic setting consumed vodka nightly for 12 days with the glycyrrhizin product or placebo (blank control), achieving a blood alcohol level of 0.12%. Liver function enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase and serum reduced glutathione were measured at overnight visits 1, 6, and 12. In the alcohol only group, AST, ALT, and GGT significantly increased from baseline (overnight visit 1) to overnight visit 12. In the active group, no statistically significant increases were observed for AST, ALT, and GGT, while alkaline phosphatase significantly decreased and plasma glutathione decreased relative to the alcohol control group. These results suggest that consumption of the proprietary glycyrrhizin study product during alcohol consumption may support improved liver health compared with drinking alcohol alone. Copyright © 2016 John Wiley & Sons, Ltd.

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Additive Effects of Mitochondrion-targeted Cytochrome CYP2E1 and Alcohol Toxicity on Cytochrome c Oxidase Function and Stability of Respirosome Complexes

Cited by 28 publications

References 79 publications

Human Cytochrome P450 2E1 Mutations That Alter Mitochondrial Targeting Efficiency and Susceptibility to Ethanol-induced Toxicity in Cellular Models

Human Cytochrome P450 2E1 Mutations That Alter Mitochondrial Targeting Efficiency and Susceptibility to Ethanol-induced Toxicity in Cellular Models

Mitochondria‐Targeted Cytochromes P450 Modulate Adverse Drug Metabolism and Xenobiotic‐Induced Toxicity

Hepatoprotective Effects of a Proprietary Glycyrrhizin Product during Alcohol Consumption: A Randomized, Double‐Blind, Placebo‐Controlled, Crossover Study

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