Journal article
Astrocyte Mitochondria Are a Sensitive Target of PCB52 and its Human-Relevant Metabolites
ACS chemical neuroscience, Vol.15(15), pp.2729-2740
07/02/2024
DOI: 10.1021/acschemneuro.4c00116
PMCID: PMC11311133
PMID: 38953493
Appears in UI Libraries Support Open Access
Abstract
Polychlorinated biphenyls (PCBs) are industrial chemicals that are ubiquitously found in the environment. Exposure to these compounds has been associated with neurotoxic outcomes; however, the underlying mechanisms for such outcomes remain to be fully understood. Recent studies have shown that astrocytes, the most abundant glial cell type in the brain, are susceptible to PCB exposure as well as exposure to human-relevant metabolites of PCBs. Astrocytes are critical for maintaining healthy brain function due to their unique functional attributes and positioning within the neuronal networks in the brain. In this study, we assessed the toxicity of PCB52, one of the most abundantly found PCB congeners in outdoor and indoor air, and two of its human-relevant metabolites, on astrocyte mitochondria. We exposed C6 cells, an astrocyte cell line, to PCB52 or its human-relevant metabolites and found that all the compounds showed increased toxicity in galactose-containing media compared to that in the glucose-containing media, indicating the involvement of mitochondria in observed toxicity. Additionally, we also found increased oxidative stress upon exposure to PCB52 metabolites. All three compounds caused a loss of mitochondrial membrane potential, distinct changes in the mitochondrial structure, and impaired mitochondrial function. The hydroxylated metabolite 4-OH-PCB52 likely functions as an uncoupler of mitochondria. This is the first study to report the adverse effects of exposure to PCB52 and its human-relevant metabolites on the mitochondrial structure and function in astrocytes.
Details
- Title: Subtitle
- Astrocyte Mitochondria Are a Sensitive Target of PCB52 and its Human-Relevant Metabolites
- Creators
- Neha Paranjape - University of Iowa, Occupational and Environmental HealthStefan Strack - University of Iowa, Iowa Neuroscience InstituteHans-Joachim Lehmler - University of Iowa, Occupational and Environmental HealthJonathan A. Doorn - University of Iowa, Medicinal and Natural Products Chemistry
- Resource Type
- Journal article
- Publication Details
- ACS chemical neuroscience, Vol.15(15), pp.2729-2740
- DOI
- 10.1021/acschemneuro.4c00116
- PMID
- 38953493
- PMCID
- PMC11311133
- NLM abbreviation
- ACS Chem Neurosci
- ISSN
- 1948-7193
- eISSN
- 1948-7193
- Publisher
- American Chemical Society
- Language
- English
- Electronic publication date
- 07/02/2024
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
- Record Identifier
- 9984650559902771
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