Cellular and Molecular Mechanisms of PCB Developmental Neurotoxicity

Panesar, Harmanpreet; Wilson, Rebecca J.; Lein, Pamela J.

doi:10.1007/978-3-030-71519-9_204-1

Cited by 2 publications

(6 citation statements)

References 52 publications

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“…The other two mixtures are composed of primarily non-dioxin-like congeners; thus, the previously proposed mechanisms are unlikely to explain the effects of Aroclor 1016 and the Cabinet Mixture. Non-dioxin-like PCBs, such as those found in Aroclor 1016 and the Cabinet Mixture, have been shown to induce neuronal apoptosis via a p53-independent mechanism . They also bind to ryanodine receptors (RyR) and increase calcium release from the endoplasmic reticulum of neurons.…”

Section: Implications For Human Healthmentioning

confidence: 99%

“…They also bind to ryanodine receptors (RyR) and increase calcium release from the endoplasmic reticulum of neurons. Increased RyR activity is associated with neuronal apoptosis and dendritic growth . In adipocytes, the RyR3 activity is inversely related to adiponectin mRNA expression; thus, overactivation of RyR by non-dioxin-like PCBs is one potential mechanism of disrupted adipose function .…”

Section: Implications For Human Healthmentioning

confidence: 99%

“…Non-dioxin-like PCBs, such as those found in Aroclor 1016 and the Cabinet Mixture, have been shown to induce neuronal apoptosis via a p53-independent mechanism. 70 They also bind to ryanodine receptors (RyR) and increase calcium release from the endoplasmic reticulum of neurons. Increased RyR activity is associated with neuronal apoptosis and dendritic growth.…”

Section: Implications For Human Healthmentioning

confidence: 99%

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Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl

Behan-Bush

Liszewski

Schrodt

et al. 2023

Environ. Sci. Technol.

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Polychlorinated biphenyl (PCB) accumulates in adipose where it may impact the growth and function of cells within the tissue. This is particularly concerning during adolescence when adipocytes expand rapidly. Herein, we sought to understand how exposure to PCB mixtures found in U.S. schools affects human adipose mesenchymal stem/stromal cell (MSC) health and function. We investigated how exposure to Aroclor 1016 and Aroclor 1254, as well as a newly characterized non-Aroclor mixture that resembles the PCB profile found in cabinets, Cabinet Mixture, affects adipose MSC growth, viability, and function in vitro. We found that exposure to all three mixtures resulted in two distinct types of toxicity. At PCB concentrations >20 μM, the majority of MSCs die, while at 1−10 μM, MSCs remained viable but display numerous alterations to their phenotype. At these sublethal concentrations, the MSC rate of expansion slowed and morphology changed. Further assessment revealed that PCB-exposed MSCs had impaired adipogenesis and a modest decrease in immunosuppressive capabilities. Thus, exposure to PCB mixtures found in schools negatively impacts the health and function of adipose MSCs. This work has implications for human health due to MSCs' role in supporting the growth and maintenance of adipose tissue.

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Section: Implications For Human Healthmentioning

confidence: 99%

Section: Implications For Human Healthmentioning

confidence: 99%

Section: Implications For Human Healthmentioning

confidence: 99%

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Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl

Behan-Bush

Liszewski

Schrodt

et al. 2023

Environ. Sci. Technol.

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show abstract

“…Non-dioxin-like PCBs, such as those found in Aroclor 1016 and Cabinet Mixture, have been shown to induce neuronal apoptosis via a p53-independent mechanism. 62 They also bind to ryanodine receptors (RyR) and increase calcium release from the endoplasmic reticulum of neurons. Increased RyR activity is associated with neuronal apoptosis and dendritic growth.…”

Section: Implications For Human Healthmentioning

confidence: 99%

“…Increased RyR activity is associated with neuronal apoptosis and dendritic growth. 62 In adipocytes, RyR3 activity is inversely related to adiponectin mRNA expression, thus overactivation of RyR by non-dioxin-like PCBs is one potential mechanism of disrupted adipose function. 63 While further studies will be required to understand which congeners or congener interactions are responsible for toxicity and their mechanisms of action, this work provides direct evidence that short-term exposure to environmentally relevant mixtures of PCBs disrupt the health and function of adipose MSCs.…”

Section: Implications For Human Healthmentioning

confidence: 99%

Toxicity impacts on human adipose MSCs acutely exposed to Aroclor and non-Aroclor mixtures of PCBs

Behan-Bush

Liszewski

Schrodt

et al. 2022

Preprint

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PCBs accumulate in adipose where they may impact the growth and function of cells within the tissue. This is particularly concerning during adolescence when adipocytes expand rapidly. Herein we sought to understand how exposure to PCB mixtures found in U.S. schools affects human adipose mesenchymal stem/stromal cell (MSC) health and function. We investigated how exposure to Aroclor 1016 and Aroclor 1254, as well as a newly characterized non-Aroclor mixture that resembles the PCB profile found in cabinets, Cabinet Mixture, affects adipose MSC growth, viability, and function in vitro. We found that exposure to all three mixtures resulted in two distinct types of toxicity. At PCB concentrations >20 μM, the majority of MSCs die, while at 1-10 μM MSCs remained viable but display numerous alterations to their phenotype. At these sublethal concentrations, MSC rate of expansion slowed, and morphology changed. Further assessment revealed PCB-exposed MSCs had impaired adipogenesis and a modest decrease in immunosuppressive capabilities. Thus, exposure to PCB mixtures found in schools negatively impacts the health and function of adipose MSCs. This work has implications for human health due to MSCs role in supporting the growth and maintenance of adipose tissue.

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Cellular and Molecular Mechanisms of PCB Developmental Neurotoxicity

Cited by 2 publications

References 52 publications

Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl

Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl

Toxicity impacts on human adipose MSCs acutely exposed to Aroclor and non-Aroclor mixtures of PCBs

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