pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na/K-ATPase/ROS Amplification in C57Bl6 and ApoE Knockout Mice Fed a Western Diet
Authors: Zijian Xie
Rebecca Martin
Saroj Sigdel
Muhammad Chaudhry
Joseph I Shapiro
Perrine Goguet-Rubio
Nader G Abraham
Mehiar El-Hamdani
Komal Sodhi
Jiang Liu
Alexandra Nichols
Preeya T Shah
Amrita Mallick
Athar Nawab
Krithika Srikanthan
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: Na/K-ATPase; ROS amplification; pNaKtide; steatohepatitis; NASH
Affiliations: 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., Departments of Medicine, Surgery, Pathology, and Cardiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA. .

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. 

Retracted: Yes

PubPeer comments:
 ![file] Figure 3B-actin and FIgure 3C porin are the same. , 
 The panels in figure 2 that show the ponceau S staining of gels run on extracts of the two mouse strains (C57Bl6 and ApoEu2212 u2212) appear to be images of the same gel. However, the aspect ratio and the brightness of the images are different. Perhaps the authors can comment. ![file] ![file] , 
 Note also in Figure 2 that the original gel appears to have had only three lanes, as identified by their spots. A similar phenomenon can be seen in another Coomassie stained gel in a paper by the same authors in 2018. In this case two lanes have been expanded into 8 lanes by reflection both ways, again as identified by their spots ![file] This is part of Figure 3H of this paper: The Na K-ATPase Oxidant Amplification Loop Regulates Aging Komal Sodhi, Alexandra Nichols, Amrita Mallick, Rebecca L. Klug, Jiang Liu, Xiaoliang Wang, Krithika Srikanthan, Perrine Goguet-Rubio, Athar Nawab, Rebecca Pratt, Megan N. Lilly, Juan R. Sanabria, Zijian Xie, Nader G. Abraham Joseph I. Shapiro Scientific Reports (2018) 8:9721 | DOI:10.1038 s41598-018-26768-9 , 
 And also, Ponceau S stains Red.... , 
 I too noticed the color of the gel, Purple Sponge. But I figured, red, blue, what s the difference? There is one other thing I noticed, but was a bit unsure about. It appears to me that the left three lanes and the right three lanes in each gel are, to use a phrase from Dr. Bik, more similar than expected. Is it possible that two six lane gels were derived from three lanes? , 
 Sci Rep. 2022 May 30;12(1):9006. doi: 10.1038 s41598-022-13458-w. Retraction Note Open Access Published: 30 May 2022 Retraction Note: pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na K-ATPase ROS Amplification in C57Bl6 and ApoE Knockout Mice Fed a Western Diet The Editors have retracted this Article. After publication, concerns were raised regarding high similarity in images used in the figures presented in this Article. Specifically: Ponceau S staining images in Fig. 2a and b Ponceau S staining images in Fig. 2 between lanes 1u20133 and lanes 4u20136 Western blots presented for Actin in Fig. 3b and Porin in 3c The Editors therefore no longer have confidence in the presented data. Nader G. Abraham agrees to this retraction. Komal Sodhi, Rebecca Martin, Preeya T. Shah, Muhammad Chaudhry, Jiang Liu, and Joseph I. Shapiro do not agree to this retraction. Krithika Srikanthan, Perrine Goguet-Rubio, Alexandra Nichols, Amrita Mallick, Athar Nawab, Saroj Sigdel, Mehiar El-Hamdani, and Zijian Xie have not responded to any correspondence from the Editors about this retraction. , 
 https: retractionwatch.com 2022 06 08 medical-school-dean-up-to-five-retractions https: forbetterscience.com 2021 04 13 the-intellectual-leaps-of-joe-shapiro ,