Cardiac-specific overexpression of catalase attenuates paraquat-induced myocardial geometric and contractile alteration: role of ER stress.

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