4,4′‐Dichlorodiphenyltrichloroethane (<scp>DDT</scp>) and 4,4′‐dichlorodiphenyldichloroethylene (<scp>DDE</scp>) inhibit myogenesis in <scp>C2C12</scp> myoblasts

Kim, Jonggun; Park, Min Young; Kim, Yoo; Yoon, Kyong Sup; Clark, J. Marshall; Park, Yeonhwa; Whang, Kwang Youn

doi:10.1002/jsfa.8399

Cited by 5 publications

(1 citation statement)

References 45 publications

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“…Currently, numerous RyR1 congenital myopathies, that typically confer a gain-of-function, have been identified (Lawal et al, 2018;Witherspoon and Meilleur, 2016), and they are well known to cause clinical neuromuscular issues. DDx has also been shown to impair myogenesis doseand time-dependently (Kim et al, 2017), and this in combination with its ability to modulate RyR1 activity to cause Ca 2þ dysregulation in muscle cells can lead to exacerbation of muscle impairments in not only populations with RyR1 congenital myopathies, but also in healthy individuals. Therefore, further studies are warranted to investigate how DDx differentially affects both population of individuals.…”

Section: Discussionmentioning

confidence: 99%

Interactions of Dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) With Skeletal Muscle Ryanodine Receptor Type 1

Truong

Cherednichenko

Pessah

2019

Toxicological Sciences

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Dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) are ubiquitous in the environment and detected in tissues of living organisms. Although DDT owes its insecticidal activity to impeding closure of voltage-gated sodium channels, it mediates toxicity in mammals by acting as an endocrine disruptor (ED). Numerous studies demonstrate DDT/DDE to be EDs, but studies examining muscle-specific effects mediated by nonhormonal receptors in mammals are lacking. Therefore, we investigated whether o,p′-DDT, p,p′-DDT, o,p′-DDE, and p,p′-DDE (DDx, collectively) alter the function of ryanodine receptor type 1 (RyR1), a protein critical for skeletal muscle excitation-contraction coupling and muscle health. DDx (0.01–10 µM) elicited concentration-dependent increases in [3H]ryanodine ([3H]Ry) binding to RyR1 with o,p′-DDE showing highest potency and efficacy. DDx also showed sex differences in [3H]Ry-binding efficacy toward RyR1, where [3H]Ry-binding in female muscle preparations was greater than male counterparts. Measurements of Ca2+ transport across sarcoplasmic reticulum (SR) membrane vesicles further confirmed DDx can selectively engage with RyR1 to cause Ca2+ efflux from SR stores. DDx also disrupts RyR1-signaling in HEK293T cells stably expressing RyR1 (HEK-RyR1). Pretreatment with DDx (0.1–10 µM) for 100 s, 12 h, or 24 h significantly sensitized Ca2+-efflux triggered by RyR agonist caffeine in a concentration-dependent manner. o,p′-DDE (24 h; 1 µM) significantly increased Ca2+-transient amplitude from electrically stimulated mouse myotubes compared with control and displayed abnormal fatigability. In conclusion, our study demonstrates DDx can directly interact and modulate RyR1 conformation, thereby altering SR Ca2+-dynamics and sensitize RyR1-expressing cells to RyR1 activators, which may ultimately contribute to long-term impairments in muscle health.

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Section: Discussionmentioning

confidence: 99%

Interactions of Dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) With Skeletal Muscle Ryanodine Receptor Type 1

Truong

Cherednichenko

Pessah

2019

Toxicological Sciences

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Transcriptome signatures of p,p´-DDE-induced liver damage in Mus spretus mice

Morales-Prieto

Ruiz-Laguna

Sheehan

et al. 2018

Environmental Pollution

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Permethrin and ivermectin modulate lipid metabolism in steatosis-induced HepG2 hepatocyte

Yang

Farias-Pereira

et al. 2019

Food and Chemical Toxicology

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Recent studies have reported the positive association between exposure to insecticides and increased risk of obesity and type 2 diabetes, which are closely associated with non-alcoholic fatty liver disease (NAFLD). However, it is not known if insecticide exposure can contribute to NAFLD. Thus, the goal of the current study was to determine if insecticide exposures can exacerbate the physiological conditions of NAFLD by modulating hepatic lipid metabolism. The effects of 12 insecticides on triglycerides (TG) accumulation were tested using palmitic acid (PA)induced HepG2 hepatoma steatosis model. Results showed that among tested insecticides, permethrin and ivermectin significant interacted with palmitic acid to potentiate (permethrin) or decrease (ivermectin) TG accumulation. Further study showed that permethrin significantly promoted fatty acid synthesis, while suppressed lipid oxidation-related genes only under steatosis conditions. In comparison, ivermectin inhibited lipogenesis-related genes and promoted farnesoid X receptor, which upregulates fatty acid oxidation. Results in this study suggested that hepatic lipid metabolism may be more susceptible to insecticide exposure in the presence of excessive fatty acids, which can be associated with the development of NAFLD.

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4,4′‐Dichlorodiphenyltrichloroethane (DDT) and 4,4′‐dichlorodiphenyldichloroethylene (DDE) inhibit myogenesis in C2C12 myoblasts

Abstract: These results may have significant implications for understanding the effects of developmental exposure of DDT and DDE on myogenesis and development of obesity and type 2 diabetes later in life. © 2017 Society of Chemical Industry.

Cited by 5 publications

References 45 publications

Interactions of Dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) With Skeletal Muscle Ryanodine Receptor Type 1

Interactions of Dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) With Skeletal Muscle Ryanodine Receptor Type 1

Transcriptome signatures of p,p´-DDE-induced liver damage in Mus spretus mice

Permethrin and ivermectin modulate lipid metabolism in steatosis-induced HepG2 hepatocyte

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