title: pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na/K-ATPase/ROS Amplification in C57Bl6 and ApoE Knockout Mice Fed a Western Diet.
abstract: We have previously reported that the α1 subunit of sodium potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a "western" diet containing high amounts of fat and fructose. The administration of pNaKtide reduced obesity as well as hepatic steatosis, inflammation and fibrosis. Of interest, we also noted marked improvement in mitochondrial fatty acid oxidation, insulin sensitivity, dyslipidemia and aortic streaking in this mouse model. To further elucidate the effects of pNaKtide on atherosclerosis, similar studies were performed in ApoE knockout mice also exposed to the western diet. In these mice, pNaKtide not only improved steatohepatitis, dyslipidemia, and insulin sensitivity, but also ameliorated significant aortic atherosclerosis. Collectively, this study demonstrates that the Na/K-ATPase/ROS amplification loop contributes significantly to the development and progression of steatohepatitis and atherosclerosis. And furthermore, this study presents a potential treatment, the pNaKtide, for the metabolic syndrome phenotype.
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Komal
authors.initials: K
authors.lastname: Sodhi
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Krithika
authors.initials: K
authors.lastname: Srikanthan
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Perrine
authors.initials: P
authors.lastname: Goguet-Rubio
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nichols
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Mallick
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Athar
authors.initials: A
authors.lastname: Nawab
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Martin
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Preeya T
authors.initials: PT
authors.lastname: Shah
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Muhammad
authors.identifier: 0000-0002-6744-8841
authors.initials: M
authors.lastname: Chaudhry
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Saroj
authors.initials: S
authors.lastname: Sigdel
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Mehiar
authors.identifier: 0000-0003-0066-9997
authors.initials: M
authors.lastname: El-Hamdani
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA.|Department of Medicine, New York Medical College, Valhalla, NY, 10595, USA.
authors.forename: Nader G
authors.initials: NG
authors.lastname: Abraham
authors.affiliation: Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA. shapiroj@marshall.edu.
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D066273:Diet, Western / Q000009:adverse effects; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D009929:Organ Size / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D050151:Subcutaneous Fat / Q000187:drug effects
chemical_list: C544203:NaKtide; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D000254:Sodium-Potassium-Exchanging ATPase