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Full-Text Articles in Medical Sciences
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
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 …
Marinobufagenin Stimulates Fibroblast Collagen Production And Causes Fibrosis In Experimental Uremic Cardiomyopathy, Jihad Elkareh, David Kennedy, Belvadi Yashaswi, Sandeep Vetteth, Amjad Shidyak, Eric Kim, Sleiman Smaili, Sankaridrug Periyasamy, Imad Hariri, Larisa Fedorova, Jiang Liu, Liang Wu, M. Kahaleh, Zijian Xie, Deepak Malhotra, Olga Fedorova, Vladimir Kashkin, Alexei Bagrov, Joseph Shapiro
Marinobufagenin Stimulates Fibroblast Collagen Production And Causes Fibrosis In Experimental Uremic Cardiomyopathy, Jihad Elkareh, David Kennedy, Belvadi Yashaswi, Sandeep Vetteth, Amjad Shidyak, Eric Kim, Sleiman Smaili, Sankaridrug Periyasamy, Imad Hariri, Larisa Fedorova, Jiang Liu, Liang Wu, M. Kahaleh, Zijian Xie, Deepak Malhotra, Olga Fedorova, Vladimir Kashkin, Alexei Bagrov, Joseph Shapiro
Zijian Xie
We have observed recently that experimental renal failure in the rat is accompanied by increases in circulating concentrations of the cardiotonic steroid, marinobufagenin (MBG), and substantial cardiac fibrosis. We performed the following studies to examine whether MBG might directly stimulate cardiac fibroblast collagen production. In vivo studies were performed using the 5/6th nephrectomy model of experimental renal failure (PNx), MBG infusion (MBG), PNx after immunization against MBG, and concomitant PNx and adrenalectomy. Physiological measurements with a Millar catheter and immunohistochemistry were performed. In vitro studies were then pursued with cultured isolated cardiac fibroblasts. We observed that PNx and MBG increased …
Spironolactone Attenuates Experimental Uremic Cardiomyopathy By Antagonizing Marinobufagenin, Jiang Tian, Amjad Shidyak, Sankaridrug Periyasamy, Steven Haller, Mohamed Taleb, Nasser El-Okdi, Jihad Elkareh, Shalini Gupta, Sabry Gohara, Olga Fedorova, Christopher Cooper, Zijian Xie, Deepak Malhorta, Alexei Bagrov, Joseph Shapiro
Spironolactone Attenuates Experimental Uremic Cardiomyopathy By Antagonizing Marinobufagenin, Jiang Tian, Amjad Shidyak, Sankaridrug Periyasamy, Steven Haller, Mohamed Taleb, Nasser El-Okdi, Jihad Elkareh, Shalini Gupta, Sabry Gohara, Olga Fedorova, Christopher Cooper, Zijian Xie, Deepak Malhorta, Alexei Bagrov, Joseph Shapiro
Zijian Xie
Spironolactone has been noted to attenuate cardiac fibrosis. We have observed that the cardiotonic steroid marinobufagenin plays an important role in the diastolic dysfunction and cardiac fibrosis seen with experimental renal failure. We performed the following studies to determine whether and how spironolactone might ameliorate these changes. First, we studied rats subjected to partial nephrectomy or administration of exogenous marinobufagenin. We found that spironolactone (20 mg/kg per day) attenuated the diastolic dysfunction as assessed by ventricular pressure-volume loops and essentially eliminated cardiac fibrosis as assessed by trichrome staining and Western blot. Next, we examined the effects of spironolactone and its …
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
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 …