Original ContributionCardiac-specific overexpression of catalase attenuates paraquat-induced myocardial geometric and contractile alteration: Role of ER stress
Section snippets
Experimental animals and paraquat treatment
The experimental protocol described in this study was approved by the Animal Use and Care Committees at the University of Wyoming (Laramie, WY, USA). Cardiac-specific overexpression catalase mice were used as described [20], [21]. FVB littermates were used as wild type. A primer pair derived from the MHC promoter and rat catalase cDNA was used for identification of the catalase transgene, with the reverse sequence of 5′-AATATCGTGGGTGACCTCAA-3′ and the forward sequence of
Echocardiographic properties of FVB and catalase mice with or without paraquat treatment
Measurement of catalase activity revealed significantly elevated enzymatic activity only in hearts and not in brain, liver, kidney, or skeletal muscles (gastrocnemius) (Fig. 1), validating the cardiac specificity of the transgene overexpression. Heart rate and LV wall thickness were not significantly affected by the catalase transgene or paraquat treatment. Paraquat significantly increased EDD, ESD, and calculated LV mass as well as suppressing fractional shortening in FVB mice. Catalase
Discussion
Data from this study revealed that the antioxidant catalase mitigated the herbicide pro-oxidant paraquat-induced cardiac geometric alteration, myocardial contractile dysfunction, apoptosis, and ER stress. In addition, paraquat-induced cardiomyocyte dysfunction was mitigated by the ER stress inhibitor tauroursodeoxycholic acid, whereas the JNK inhibitor SP600125 reversed paraquat-induced ER stress. These findings support the previous observation that paraquat exerts devastating cardiac anomalies
Acknowledgments
This work was presented in part in abstract form during Experimental Biology 2010 in Anaheim, California, USA. The founder mice of the catalase transgenic line were kindly provided by Professor Paul N. Epstein from the University of Louisville (Louisville, KY, USA). This work was supported in part by NIH 1R01 AA013412 and 5P20 RR016474 (J.R.).
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