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Medical Biochemistry Commons

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Full-Text Articles in Medical Biochemistry

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md Jun 2016

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Zijian Xie

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice fed …


Identification Of Hydroxyxanthones As Na/K-Atpase Ligands, Zhongbing Zhang, Zhichuan Li, Jiang Tian, Wei Jiang, Yin Wang, Xiaojin Zhang, Zhuorong Li, Qidong You, Joseph Shapiro, Shuyi Si, Zijian Xie Oct 2015

Identification Of Hydroxyxanthones As Na/K-Atpase Ligands, Zhongbing Zhang, Zhichuan Li, Jiang Tian, Wei Jiang, Yin Wang, Xiaojin Zhang, Zhuorong Li, Qidong You, Joseph Shapiro, Shuyi Si, Zijian Xie

Zijian Xie

We have screened a chemical library and identified several novel structures of Na/K-ATPase inhibitors. One group of these inhibitors belongs to polyphenolic xanthone derivatives. Functional characterization reveals the following properties of this group of inhibitors. First, like ouabain, they are potent inhibitors of the purified Na/K-ATPase. Second, their effects on the Na/K-ATPase depend on the number and position of phenolic groups. Methylation of these phenolic groups reduces the inhibitory effect. Third, further characterization of the most potent xanthone derivative, MB7 (3,4,5,6-tetrahydroxyxanthone), reveals that it does not change either Na+ or ATP affinity of the enzyme. Finally, unlike that of …


Central Role For The Cardiotonic Steroid Marinobufagenin In The Pathogenesis Of Experimental Uremic Cardiomyopathy, David Kennedy, Sandeep Vetteth, Sankaridrug Periyasamy, Mohamed Kanj, Larisa Fedorova, Samer Khouri, M. Kahaleh, Zijian Xie, Deepak Malhotra, Nikolai Kolodkin, Edward Lakatta, Olga Fedorova, Alexei Bagrov, Joseph Shapiro Oct 2015

Central Role For The Cardiotonic Steroid Marinobufagenin In The Pathogenesis Of Experimental Uremic Cardiomyopathy, David Kennedy, Sandeep Vetteth, Sankaridrug Periyasamy, Mohamed Kanj, Larisa Fedorova, Samer Khouri, M. Kahaleh, Zijian Xie, Deepak Malhotra, Nikolai Kolodkin, Edward Lakatta, Olga Fedorova, Alexei Bagrov, Joseph Shapiro

Zijian Xie

Patients with chronic renal failure develop a “uremic” cardiomyopathy characterized by diastolic dysfunction, cardiac hypertrophy, and systemic oxidant stress. Patients with chronic renal failure are also known to have increases in the circulating concentrations of the cardiotonic steroid marinobufagenin (MBG). On this background, we hypothesized that elevations in circulating MBG may be involved in the cardiomyopathy. First, we observed that administration of MBG (10 g/kg per day) for 4 weeks caused comparable increases in plasma MBG as partial nephrectomy at 4 weeks. MBG infusion caused increases in conscious blood pressure, cardiac weight, and the time constant for left ventricular relaxation …


Marinobufagenin Induces Increases In Procollagen Expression In A Process Involving Protein Kinase C And Fli-1: Implications For Uremic Cardiomyopathy, Jihad Elkareh, Sankaridrug Periyasamy, Amjad Shidyak, Sandeep Vetteth, Jeremy Schroeder, Vanamala Raju, Imad Hariri, Nasser El-Okdi, Shalini Gupta, Larisa Fedorova, Jiang Liu, Olga Fedorova, M. Kahaleh, Zijian Xie, Deepak Malhotra, Dennis Watson, Alexei Bagrov, Joseph Shapiro Sep 2015

Marinobufagenin Induces Increases In Procollagen Expression In A Process Involving Protein Kinase C And Fli-1: Implications For Uremic Cardiomyopathy, Jihad Elkareh, Sankaridrug Periyasamy, Amjad Shidyak, Sandeep Vetteth, Jeremy Schroeder, Vanamala Raju, Imad Hariri, Nasser El-Okdi, Shalini Gupta, Larisa Fedorova, Jiang Liu, Olga Fedorova, M. Kahaleh, Zijian Xie, Deepak Malhotra, Dennis Watson, Alexei Bagrov, Joseph Shapiro

Zijian Xie

The cardiotonic steroid marinobufagenin (MBG) has been implicated in the pathogenesis of experimental uremic cardiomyopathy, which is characterized by progressive cardiac fibrosis. We examined whether the transcription factor Friend leukemia integration-1 (Fli-1) might be involved in this process. Fli-1-knockdown mice demonstrated greater cardiac collagen-1 expression and fibrosis compared with wild-type mice; both developed increased cardiac collagen expression and fibrosis after 5/6 nephrectomy. There was a strong inverse relationship between the expressions of Fli-1 and procollagen in primary culture of rat cardiac and human dermal fibroblasts as well as a cell line derived from renal fibroblasts and MBG-induced decreases in nuclear …