ArticleToxicology2017
1,3-Butadiene-induced mitochondrial dysfunction is correlated with mitochondrial CYP2E1 activity in Collaborative Cross mice.
Article in Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Exposure to volatile organic compounds increases the risk of sarcopenia: Insights into association and mechanism.PloS one · 2025Article
- Transgenic expression of human cytochrome P450 2E1 in C. elegans and rat PC-12 cells sensitizes to ethanol-induced locomotor and mitochondrial effects.Biochemical and biophysical research communications · 2024Article
- Subcellular expression of CYP2E1 in HepG2 cells impacts response to free oleic and palmitic acid.Current research in toxicology · 2024Article
- Review
- Lung metabolome of 1,3-butadiene exposed Collaborative Cross mice reflects metabolic phenotype of human lung cancer.Toxicology · 2021Article
- The Multifarious Link between Cytochrome P450s and Cancer.Oxidative medicine and cellular longevity · 2020Review
- Using Collaborative Cross Mouse Population to Fill Data Gaps in Risk Assessment: A Case Study of Population-Based Analysis of Toxicokinetics and Kidney Toxicodynamics of Tetrachloroethylene.Environmental health perspectives · 2019Article
- Population-Based Analysis of DNA Damage and Epigenetic Effects of 1,3-Butadiene in the Mouse.Chemical research in toxicology · 2019Article
- Whole Genome Sequencing and Progress Toward Full Inbreeding of the Mouse Collaborative Cross Population.G3 (Bethesda, Md.) · 2019Article
- Sex-specific differences in genotoxic and epigenetic effects of 1,3-butadiene among mouse tissues.Archives of toxicology · 2019Article
- Zebrafish have an ethanol-inducible hepatic 4-nitrophenol hydroxylase that is not CYP2E1-like.Environmental toxicology and pharmacology · 2017Article
- New Rodent Population Models May Inform Human Health Risk Assessment and Identification of Genetic Susceptibility to Environmental Exposures.Environmental health perspectives · 2017Review
- Toxicological Implications of Mitochondrial Localization of CYP2E1.Toxicology research · 2017Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Cytochrome P450 2E1 (CYP2E1) metabolizes low molecular weight hydrophobic compounds, including 1,3-butadiene, which is converted by CYP2E1 to electrophilic epoxide metabolites that covalently modify cellular proteins and DNA. Previous CYP2E1 studies have mainly focused on the enzyme localized in the endoplasmic reticulum (erCYP2E1); however, active CYP2E1 has also been found in mitochondria (mtCYP2E1) and the distribution of CYP2E1 between organelles can influence an individual's response to exposure. Relatively few studies have focused on the contribution of mtCYP2E1 to activation of chemical toxicants. We hypothesized that CYP2E1 bioactivation of 1,3-butadiene within mitochondria adversely affects mitochondrial respiratory complexes I-IV. A population of Collaborative Cross mice was exposed to air (control) or 200ppm 1,3-butadiene. Subcellular fractions (mitochondria, DNA, and microsomes) were collected from frozen livers and CYP2E1 activity was measured in microsomes and mitochondria. Individual activities of mitochondrial respiratory complexes I-IV were measured using in vitro assays and purified mitochondrial fractions. In air- and 1,3-butadiene-exposed mouse samples, mtDNA copy numbers were assessed by RT-PCR, and mtDNA integrity was assessed through a PCR-based assay. No significant changes in mtDNA copy number or integrity were observed; however, there was a decrease in overall activity of mitochondrial respiratory complexes I, II, and IV after 1,3-butadiene exposure. Additionally, higher mtCYP2E1 (but not erCYP2E1) activity was correlated with decreased mitochondrial respiratory complex activity (in complexes I-IV) in the 1,3-butadiene-exposed (not control) animals. Together, these results represent the first in vivo link between mitochondrial CYP2E1 activity and mitochondrial toxicity.
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