title: Attenuation of Na/K-ATPase Mediated Oxidant Amplification with pNaKtide Ameliorates Experimental Uremic Cardiomyopathy.
abstract: We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic cardiomyopathy reversed many of the phenotypical features. Attenuation of Na/K-ATPase oxidant amplification may be a potential strategy for clinical therapy of this disorder.
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: University of Toledo, College of Medicine, 3000 Arlington Ave. Toledo, OH 43614 United States.
authors.forename: Jiang
authors.initials: J
authors.lastname: Tian
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Chaudhry
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Kyle
authors.initials: K
authors.lastname: Maxwell
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Preeya T
authors.initials: PT
authors.lastname: Shah
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Asad A
authors.initials: AA
authors.lastname: Khawaja
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Martin
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Tylor J
authors.initials: TJ
authors.lastname: Robinette
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Adee
authors.initials: A
authors.lastname: El-Hamdani
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Dodrill
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Komal
authors.initials: K
authors.lastname: Sodhi
authors.affiliation: University of Toledo, College of Medicine, 3000 Arlington Ave. Toledo, OH 43614 United States.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Drummond
authors.affiliation: University of Toledo, College of Medicine, 3000 Arlington Ave. Toledo, OH 43614 United States.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Haller
authors.affiliation: University of Toledo, College of Medicine, 3000 Arlington Ave. Toledo, OH 43614 United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kennedy
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.|New York Medical College, 15 Dana Road, Valhalla, NY 10595-1554 United States.
authors.forename: Nader G
authors.initials: NG
authors.lastname: Abraham
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Marshall University, Joan C. Edwards School of Medicine, 1600 Medical Center Drive Huntington, 25701 United States.
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000628:therapy*; D004195:Disease Models, Animal; D020536:Enzyme Activators / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D016877:Oxidants / Q000378:metabolism*; D011524:Protoporphyrins / Q000008:administration & dosage; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016896:Treatment Outcome; D014511:Uremia / Q000150:complications*
chemical_list: D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D016877:Oxidants; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1; D000254:Sodium-Potassium-Exchanging ATPase