Dataset Information

Toxicological Implications of Mitochondrial Localization of CYP2E1.

ABSTRACT: Cytochrome P450 2E1 (CYP2E1) metabolizes an extensive array of pollutants, drugs, and other small molecules, often resulting in bioactivation to reactive metabolites. Therefore, it is unsurprising that it has been the subject of decades of research publications and reviews. However, while CYP2E1 has historically been studied in the endoplasmic reticulum (erCYP2E1), active CYP2E1 is also present in mitochondria (mtCYP2E1). Relatively few studies have specifically focused on mtCYP2E1, but there is growing interest in this form of the enzyme as a driver in toxicological mechanisms given its activity and location. Many previous studies have linked total CYP2E1 to conditions that involve mitochondrial dysfunction (fasting, diabetes, non-alcoholic steatohepatitis, and obesity). Furthermore, a large number of reactive metabolites that are formed by CYP2E1 through metabolism of drugs and pollutants have been demonstrated to cause mitochondrial dysfunction. Finally, there appears to be significant inter-individual variability in targeting to the mitochondria, which could constitute a source of variability in individual response to exposures. This review discusses those outcomes, the biochemical properties and toxicological consequences of mtCYP2E1, and highlights important knowledge gaps and future directions. Overall, we feel that this exciting area of research is rich with new and important questions about the relationship between mtCYP2E1, mitochondrial dysfunction, and pathology.

SUBMITTER: Hartman JH

PROVIDER: S-EPMC5627779 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Nano-enabled thermoplastics are part of the growing market of nano-enabled products (NEPs) that have vast utility in several industries and consumer goods. The use and disposal of NEPs at their end of life has raised concerns about the potential release of constituent engineered nanomaterials (ENMs) during thermal decomposition and their impact on environmental health and safety. To investigate this issue, industrially relevant nano-enabled thermoplastics including polyurethane, polycarbonate, and polypropylene containing carbon nanotubes (0.1 and 3% w/v, respectively), polyethylene containing nanoscale iron oxide (5% w/v), and ethylene vinyl acetate containing nanoscale titania (2 and 5% w/v) along with their pure thermoplastic matrices were thermally decomposed using the recently developed lab based Integrated Exposure Generation System (INEXS). The life cycle released particulate matter (called LCPM) was monitored using real time instrumentation, size fractionated, sampled, extracted and prepared for toxicological analysis using primary small airway epithelial cells to assess potential toxicological effects. Various cellular assays were used to assess reactive oxygen species and total glutathione as measurements of oxidative stress along with mitochondrial function, cellular viability, and DNA damage. By comparing toxicological profiles of LCPM released from polymer only (control) with nano-enabled LCPM, potential nanofiller effects due to the use of ENMs were determined. We observed associations between NEP properties such as the percent nanofiller loading, host matrix, and nanofiller chemical composition and the physico-chemical properties of released LCPM, which were linked to biological outcomes. More specifically, an increase in percent nanofiller loading promoted a toxicological response independent of increasing LCPM dose. Importantly, differences in host matrix and nanofiller composition were shown to enhance biological activity and toxicity of LCPM. This work highlights the importance of assessing the toxicological properties of LCPM and raises environmental health and safety concerns of nano-enabled products at their end of life during thermal decomposition/incineration.

Dataset Information

Toxicological Implications of Mitochondrial Localization of CYP2E1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets