The Na/K-ATPase Oxidant Amplification Loop Regulates Aging
Authors: Rebecca L Klug
Zijian Xie
Athar Nawab
Joseph I Shapiro
Perrine Goguet-Rubio
Nader G Abraham
Rebecca Pratt
Megan N Lilly
Komal Sodhi
Xiaoliang Wang
Jiang Liu
Juan R Sanabria
Amrita Mallick
Alexandra Nichols
Krithika Srikanthan
Journal: Scientific Reports (2018)
Discipline: Multidisciplinary
Keywords: aging; Na/K-ATPase oxidant amplification loop (NKAL); senescence markers; cell-injury; apoptosis
Affiliations: Departments of Medicine, Surgery, and Biomedical sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA., Department of Medicine and Pharmacology, New York Medical College, Valhalla, NY, 10595, USA., Departments of Medicine, Surgery, and Biomedical sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, USA. .

Abstract:  As aging involves oxidant injury, we examined the role of the recently described Na/K-ATPase oxidant amplification loop (NKAL). First, C57Bl6 old mice were given a western diet to stimulate oxidant injury or pNaKtide to antagonize the NKAL. The western diet accelerated functional and morphological evidence for aging whereas pNaKtide attenuated these changes. Next, human dermal fibroblasts (HDFs) were exposed to different types of oxidant stress in vitro each of which increased expression of senescence markers, cell-injury, and apoptosis as well as stimulated the NKAL. Further stimulation of the NKAL with ouabain augmented cellular senescence whereas treatment with pNaKtide attenuated it. Although N-Acetyl Cysteine and Vitamin E also ameliorated overall oxidant stress to a similar degree as pNaKtide, the pNaKtide produced protection against senescence that was substantially greater than that seen with either antioxidant. In particular, pNaKtide appeared to specifically ameliorate nuclear oxidant stress to a greater degree. These data demonstrate that the NKAL is intimately involved in the aging process and may serve as a target for anti-aging interventions. 

Retracted: Yes

PubPeer comments:
 Iu2019m afraid this will be difficult to explain. Figure 3H. I did not look elsewhere in this paper. *** ![file] , 
 #1 Apparently someone else found this data questionable previously: u201c07 May 2020 Editoru2019s Note: The Editors are currently investigating concerns that have been raised relating to the reliability of data presented in this article. Appropriate editorial action will be taken once the investigation is complete.u201d , 
 There are some artifacts induced on the old system we used for our Commassie staining that creates artifacts suggesting duplication of lanes. We ve noted this on internal review of our data. Unfortunately, we don t have that system anymore so we can t explore that point further. As I said in response yesterday evening to a comment about other similarities of loading control western blots, the first author and I will review all data from this paper, regardless of whether editorial staff choose to investigate. , 
 #3 I m sorry, I mispoke. We have been in communication with the editorial staff, and we have attempted to address the concerns raised about some of these data. We have repeated experiments, and we believe that we are in a position to correct figure where there were problems. Once the editorial office is satisified, we will make those corrections. , 
 #4 Thank you for your replies. This [COPE resource] may help illustrate the recommended process for addressing these concerns. , 
 #3, #4 It s not just the Coomassie data that are problematic. The same Figure 3H also has an apparent mirror-image duplication in the right-most two lanes of the DNP panel, as annotated below (with enhanced contrast): ![file] , 
 #6 Also, the Coomassie panel in Fig 6C has problems similar to those noted above in post #1 (about Fig 3H): ![file] , 
 #1, #7 It is also worth noting that the apparent duplication and mirroring in Coomassie panels of Figs 3H and 6C follow the exact same pattern. In each case it proceeds as follows: A-fwd, B-fwd, B-rev, A-rev, B-rev, A-rev, A-fwd, B-fwd Or, as seen by aligning the arrow annotations from above: ![file] , 
 Figure 3I. Much more similar than expected after horizontal flip. https: imgur.com 17loEN3 , 
 Just noticed that this paper includes a Supplement, in which several additional Figures have issues similar to those noted above. (Below, contrast has been adjusted to facilitate detection.) * Supp Fig 1A: ![file] * Supp Fig 2A: ![file] * Supp Fig 2B: ![file] , 
 Any update on this? I did not see an update on the journal site since last May. I would also appreciate it if the authors could post the original scans here. It has been only a few years since publication, so one would expect the original data would still be readily available. Repeated experiments would not address the concerns about how the original images were created. , 
 In the Western blot in figure 3I, lanes 3-5 in the lower half of the panel for src appear to be repeated in reverse in lanes 6-8 as indicated by the arrows below the images from the figure. ![file] , 
 https: www.nature.com articles s41598-022-13456-y Retraction Note: 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 volume 12, Article number: 9124 (2022) Cite this article The Original Article was published on 26 June 2018 Retraction of: Scientific Reports https: doi.org 10.1038 s41598-018-26768-9, published online 26 June 2018 The Editors have retracted this Article. After publication, concerns were raised regarding high similarity among the following: multiple lanes within each of the Coomassie blue staining images in Figs. 3h, 6c, S1a and S2a; DNP blot images in Figs. 3h (H2O2u2009+u2009pNaKtide group), S1a (both lanes in Y group and left lane in Ou2009+u2009WDu2009+u2009P group) and S2a (OB and O groups); pSRC blot images in Figs. S2b (OB group) and 3i (pNaKtide, H2O2 and H2O2u2009+u2009pNaKtide groups). Further investigation has found that there are unexplained similarities between images representing different groups in: Figs. 3a (Control and H2O2u2009+u2009pNaKtide) and S4a (Control and UVu2009+u2009pNaKtide); Fig. S3a (H2O2u2009+u2009pNaKtide 1 u03bcM and 4 u03bcM, rotated 180 degrees); Figs. S3a (H2O2 200 u03bcM) and Fig. S5a (Ouabain 1 nM). The Editors therefore no longer have confidence in the presented data. Juan R. Sanabria and Nader G. Abraham agree to this retraction. Komal Sodhi, Jiang Liu, Rebecca Pratt, and Joseph I. Shapiro do not agree to this retraction. Alexandra Nichols, Amrita Mallick, Rebecca L. Klug, Xiaoliang Wang, Krithika Srikanthan, Perrine Goguet-Rubio, Athar Nawab, Megan N. Lilly, and Zijian Xie have not responded to any correspondence from the Editors about this retraction. , 
 To the authors who did not agree with this retraction: I remain puzzled why the authors did not provide the original uncropped scans. This paper was only a couple of years old when concerns were first raised. If the lab was unable to retain records for even a handful of years, this alone is cause for alarm. , 
 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 ,