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• W1987204479 abstract "Paraquat, a quaternary nitrogen herbicide, is a highly toxic pro-oxidant that causes multiorgan failure including that of the heart via generation of reactive oxygen species, although the underlying mechanism has not been well elucidated. This study examined the influence of cardiac-specific overexpression of catalase, an antioxidant detoxifying H2O2, on paraquat-induced myocardial geometric and functional alterations, with a focus on ER stress. FVB and catalase transgenic mice were administered paraquat for 48 h. Myocardial geometry, contractile function, apoptosis, and ER stress were evaluated using echocardiography, edge detection, caspase-3 activity, and immunoblotting. Our results revealed that paraquat treatment significantly enlarged left ventricular (LV) end diastolic and systolic diameters; increased LV mass and resting myocyte length; reduced fractional shortening, cardiomyocyte peak shortening, and maximal velocity of shortening/relengthening; and prolonged relengthening duration in the FVB group. Whereas the catalase transgene itself did not alter myocardial geometry and function, it mitigated or significantly attenuated paraquat-elicited myocardial geometric and functional changes. Paraquat promoted overt apoptosis and ER stress as evidenced by increased caspase-3 activity, apoptosis, and ER stress markers including Bax, Bcl-2, GADD153, calregulin, and phosphorylated JNK, IRE1α, and eIF2α; all were ablated by the catalase transgene. Paraquat-induced cardiomyocyte dysfunction was mitigated by the ER stress inhibitor tauroursodeoxycholic acid. Moreover, the JNK inhibitor SP600125 reversed paraquat-induced ER stress as evidenced by enhanced GADD153 and IRE1α phosphorylation. Taken together, these data revealed that catalase may rescue paraquat-induced myocardial geometric and functional alteration possibly by alleviating JNK-mediated ER stress." @default.
• W1987204479 created "2016-06-24" @default.
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• W1987204479 date "2010-12-01" @default.
• W1987204479 modified "2023-10-06" @default.
• W1987204479 title "Cardiac-specific overexpression of catalase attenuates paraquat-induced myocardial geometric and contractile alteration: Role of ER stress" @default.
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• W1987204479 doi "https://doi.org/10.1016/j.freeradbiomed.2010.10.686" @default.
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