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  1. Article ; Online: Adipocyte Na, K-ATPase Signaling Attenuates Experimental Uremic Cardiomyopathy.

    Sodhi, Komal / Wang, Xiaoliang / Chaudhary, Muhammad A / Lakhani, Hari Vishal / Zehra, Mishghan / Nawab, Athar / Cottrill, Cameron L / Bai, Fang / Liu, Jiang / Sanabria, Juan R / Xie, Zijian / Shapiro, Joseph I

    Cellular and molecular biology (Noisy-le-Grand, France)

    2023  Volume 69, Issue 5, Page(s) 197–206

    Abstract: Oxidative stress has been shown to cause an alteration of intracellular signaling in adipocytes that may lead to various comorbidities of obesity and cardiovascular complications. Evidence suggests that dysregulation of Na, K-ATPase signaling can ... ...

    Abstract Oxidative stress has been shown to cause an alteration of intracellular signaling in adipocytes that may lead to various comorbidities of obesity and cardiovascular complications. Evidence suggests that dysregulation of Na, K-ATPase signaling can contribute to systemic inflammation and redox signaling that leads to various metabolic disturbances. Hence the present study aims to explore the specific role of adipocyte Na, K-ATPase signaling in the amelioration of pathophysiological alterations of experimental uremic cardiomyopathy. Experimental uremic cardiomyopathy was induced by partial nephrectomy (PNx), and adipocyte-specific expression of NaKtide, a peptide that inhibits Na, K-ATPase signaling, was achieved using a lentivirus construct with NaKtide expression driven by an adiponectin promoter. Cardiomyopathy and anemia induced in partial nephrectomy mice were accompanied by an altered molecular phenotype of adipocytes, increased systemic inflammatory cytokines and oxidant stress within 4 weeks. These changes were significantly worsened by the addition of a Western diet (enriched in fat and fructose contents) but were prevented with specific expression of NaKtide in adipocytes. The skeletal muscle-specific expression of NaKtide did not ameliorate the disease phenotype. Adipocyte dysfunction and uremic cardiomyopathy developed in PNx mice, both were significantly ameliorated by the adipocyte-specific expression of NaKtide. These findings suggest that oxidative milieu in the adipocyte has a pivotal role in the development and progression of uremic cardiomyopathy in mice subjected to partial nephrectomy. If confirmed in humans, this may be a lead for future research to explore novel therapeutic targets in chronic renal failure.
    MeSH term(s) Humans ; Mice ; Animals ; Cardiomyopathies/etiology ; Cardiomyopathies/metabolism ; Sodium-Potassium-Exchanging ATPase/metabolism ; Signal Transduction ; Oxidative Stress ; Peptides/metabolism ; Adipocytes/metabolism
    Chemical Substances Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13) ; Peptides
    Language English
    Publishing date 2023-05-31
    Publishing country France
    Document type Journal Article
    ZDB-ID 1161779-2
    ISSN 1165-158X ; 0145-5680
    ISSN (online) 1165-158X
    ISSN 0145-5680
    DOI 10.14715/cmb/2023.69.5.31
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3812: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: The Na/K-ATPase Signaling: From Specific Ligands to General Reactive Oxygen Species.

    Pratt, Rebecca D / Brickman, Cameron R / Cottrill, Cameron L / Shapiro, Joseph I / Liu, Jiang

    International journal of molecular sciences

    2018  Volume 19, Issue 9

    Abstract: The signaling function of the Na/K-ATPase has been established for 20 years and is widely accepted in the field, with many excellent reports and reviews not cited here. Even though there is debate about the underlying mechanism, the signaling function is ...

    Abstract The signaling function of the Na/K-ATPase has been established for 20 years and is widely accepted in the field, with many excellent reports and reviews not cited here. Even though there is debate about the underlying mechanism, the signaling function is unquestioned. This short review looks back at the evolution of Na/K-ATPase signaling, from stimulation by cardiotonic steroids (also known as digitalis-like substances) as specific ligands to stimulation by reactive oxygen species (ROS) in general. The interplay of cardiotonic steroids and ROS in Na/K-ATPase signaling forms a positive-feedback oxidant amplification loop that has been implicated in some pathophysiological conditions.
    MeSH term(s) Animals ; Endocytosis ; Humans ; Ligands ; Mice ; Models, Animal ; Oxidative Stress ; Potassium/metabolism ; Rats ; Reactive Oxygen Species/metabolism ; Sodium/metabolism ; Sodium-Potassium-Exchanging ATPase/metabolism
    Chemical Substances Ligands ; Reactive Oxygen Species ; Sodium (9NEZ333N27) ; Sodium-Potassium-Exchanging ATPase (EC 3.6.3.9) ; Potassium (RWP5GA015D)
    Language English
    Publishing date 2018-09-01
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms19092600
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Central Role for Adipocyte Na,K-ATPase Oxidant Amplification Loop in the Pathogenesis of Experimental Uremic Cardiomyopathy.

    Sodhi, Komal / Wang, Xiaoliang / Chaudhry, Muhammad Aslam / Lakhani, Hari Vishal / Zehra, Mishghan / Pratt, Rebecca / Nawab, Athar / Cottrill, Cameron L / Snoad, Brian / Bai, Fang / Denvir, James / Liu, Jiang / Sanabria, Juan R / Xie, Zijian / Abraham, Nader G / Shapiro, Joseph I

    publication RETRACTED

    Journal of the American Society of Nephrology : JASN

    2020  Volume 31, Issue 8, Page(s) 1746–1760

    Abstract: Background: Oxidative stress in adipocyte plays a central role in the pathogenesis of obesity as well as in the associated cardiovascular complications. The putative uremic toxin indoxyl sulfate induces oxidative stress and dramatically alters adipocyte ...

    Abstract Background: Oxidative stress in adipocyte plays a central role in the pathogenesis of obesity as well as in the associated cardiovascular complications. The putative uremic toxin indoxyl sulfate induces oxidative stress and dramatically alters adipocyte phenotype
    Methods: A lentivirus vector introduced the peptide NaKtide with an adiponectin promoter into the mouse model of experimental uremic cardiomyopathy, intraperitoneally. Then adipocyte-specific expression of the peptide was assessed for mice fed a standard diet compared with mice fed a western diet enriched in fat and fructose.
    Results: Partial nephrectomy induced cardiomyopathy and anemia in the mice, introducing oxidant stress and an altered molecular phenotype of adipocytes that increased production of systemic inflammatory cytokines instead of accumulating lipids, within 4 weeks. Consumption of a western diet significantly worsened the adipocyte oxidant stress, but expression of NaKtide in adipocytes completely prevented the worsening. The peptide-carrying lentivirus achieved comparable expression in skeletal muscle, but did not ameliorate the disease phenotype.
    Conclusions: Adipocyte-specific expression of NaKtide, introduced with a lentiviral vector, significantly ameliorated adipocyte dysfunction and uremic cardiomyopathy in partially nephrectomized mice. These data suggest that the redox state of adipocytes controls the development of uremic cardiomyopathy in mice subjected to partial nephrectomy. If confirmed in humans, the oxidative state of adipocytes may be a therapeutic target in chronic renal failure.
    MeSH term(s) Adipocytes/metabolism ; Animals ; Apoptosis ; Cardiomyopathies/etiology ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Nephrectomy ; Oxidative Stress ; Peptide Fragments/physiology ; Sodium-Potassium-Exchanging ATPase/physiology ; Uremia/complications
    Chemical Substances NaKtide ; Peptide Fragments ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
    Language English
    Publishing date 2020-06-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Retracted Publication
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2019101070
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3344: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Uremic Toxins Activates Na/K-ATPase Oxidant Amplification Loop Causing Phenotypic Changes in Adipocytes in In Vitro Models.

    Bartlett, David E / Miller, Richard B / Thiesfeldt, Scott / Lakhani, Hari Vishal / Khanal, Tilak / D Pratt, Rebecca / Cottrill, Cameron L / Klug, Rebecca L / Adkins, Nathaniel Seth / Bown, Paul C / Nease, D Blaine / Shapiro, Joseph I / Sodhi, Komal

    International journal of molecular sciences

    2018  Volume 19, Issue 9

    Abstract: Background: Oxidant stress plays a key role in the development of chronic kidney disease (CKD). Experimental CKD leads to accumulation of uremic toxins (UT) in the circulation resulting in increased ROS production, which in turn, is known to activate ... ...

    Abstract Background: Oxidant stress plays a key role in the development of chronic kidney disease (CKD). Experimental CKD leads to accumulation of uremic toxins (UT) in the circulation resulting in increased ROS production, which in turn, is known to activate the Na/K-ATPase/ROS amplification loop. Studies in a murine model of obesity have shown that increased oxidative stress in plasma is due to increased ROS and cytokine production from dysfunctional adipocytes. Therefore, we hypothesized that adipocytes exposed to UTs will activate the Na/K-ATPase oxidant amplification loop causing redox imbalance and phenotypic alterations in adipocytes. We also aimed to demonstrate that the Na/K-ATPase signaling antagonist, pNaKtide, attenuates these pathophysiological consequences.
    Methods: In the first set of experiments, 3T3-L1 murine pre-adipocytes were treated with varying concentrations of UTs, indoxyl sulfate (IS) (50, 100 and 250 µM) and p-cresol (50, 100 and 200 µM), with or without pNaKtide (0.7 µM) for five days in adipogenic media, followed by Oil Red O staining to study adipogenesis. RT-PCR analysis was performed to study expression of adipogenic, apoptotic and inflammatory markers, while DHE staining evaluated the superoxide levels in UT treated cells. In a second set of experiments, visceral fat was obtained from the West Virginian population. MSCs were isolated and cultured in adipogenic media for 14 days, which was treated with indoxyl sulfate (0, 25, 50 and 100 µM) with or without pNaKtide (1 µM). MSC-derived adipocytes were evaluated for morphological and molecular analysis of the above markers.
    Results: Our results demonstrated that 3T3-L1 cells and MSCs-derived adipocytes, treated with UTs, exhibited a significant decrease in adipogenesis and apoptosis through activation of the Na/K-ATPase/ROS amplification loop. The treatment with pNaKtide in 3T3-L1 cells and MSC-derived adipocytes negated the effects of UTs and restored cellular redox in adipocytes. We noted a varying effect of pNaKtide, in adipocytes treated with UTs, on inflammatory markers, adipogenic marker and superoxide levels in 3T3-L1 cells and MSC-derived adipocytes.
    Conclusions: This study demonstrates for the first time that the Na/K-ATPase/ROS amplification loop activated by elevated levels of UTs has varying effect on phenotypic alterations in adipocytes in various in vitro models. Thus, we propose that, if proven in humans, inhibition of Na/K-ATPase amplification of oxidant stress in CKD patients may ultimately be a novel way to combat adipocyte dysfunction and metabolic imbalance in these patients.
    MeSH term(s) 3T3-L1 Cells ; Adipocytes/cytology ; Adipocytes/drug effects ; Adipocytes/metabolism ; Animals ; Biomarkers/analysis ; Cell Proliferation/drug effects ; Cell Survival ; Cells, Cultured ; Cresols/toxicity ; Cresols/urine ; Humans ; Indican/toxicity ; Indican/urine ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/drug effects ; Mice ; Oxidants/metabolism ; Oxidative Stress ; Peptide Fragments/pharmacology ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/urine ; Sodium-Potassium-Exchanging ATPase/metabolism ; Sodium-Potassium-Exchanging ATPase/pharmacology
    Chemical Substances Biomarkers ; Cresols ; NaKtide ; Oxidants ; Peptide Fragments ; 4-cresol (1MXY2UM8NV) ; Sodium-Potassium-Exchanging ATPase (EC 3.6.3.9) ; Indican (N187WK1Y1J)
    Language English
    Publishing date 2018-09-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms19092685
    Database MEDical Literature Analysis and Retrieval System OnLINE

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