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Ryanodine Receptor Type 2: A Molecular Target for Dichlorodiphenyltrichloroethane- and Dichlorodiphenyldichloroethylene-Mediated Cardiotoxicity.


ABSTRACT: Dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyl-dichloroethylene (DDE) are ubiquitously found in the environment and linked to cardiovascular diseases-with a majority of the work focused on hypertension. Studies investigating whether DDx can interact with molecular targets on cardiac tissue to directly affect cardiac function are lacking. Therefore, we investigated whether o,p'-DDT, p,p'-DDT, o,p'-DDE, or p,p'-DDE (DDx, collectively) can directly alter the function of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) by assessing their effect(s) on hiPSC-CMs Ca2+ dynamics. DDx (0.1-10 µM) affected hiPSC-CMs synchronous Ca2+ oscillation frequency in a concentration-dependent manner, with p,p'-DDT and p,p'-DDE also decreasing Ca2+ stores. HEK-Ry

SUBMITTER: Truong KM 

PROVIDER: S-EPMC7850024 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature