A novel endogenous digitalis, telocinobufagin, exhibits elevated plasma levels in patients with terminal renal failure

Komiyama, Yutaka; Dong, Xian; Nishimura, Noriko; Masaki, Hiroya; Yoshika, Masamichi; Masuda, Midori; Takahashi, Hakuo

doi:10.1016/j.clinbiochem.2004.08.005

Cited by 138 publications

(142 citation statements)

References 35 publications

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“…132 As mentioned earlier, plasma levels of telocinobufagin and marinobufagenin are substantially elevated in patients with end-stage renal disease. 15,53 To examine the role of cardiotonic steroids in renal disease, our laboratory has established models of chronic kidney disease by the use of partial nephrectomy in the rat 133 and, more recently, the mouse. 134 Animals subjected to partial nephrectomy develop increases in marinobufagenin (similar to those seen in patients with renal disease) and diastolic dysfunction, ventricular hypertrophy, and evidence of signaling through the Na + /K + -ATPase-Src-EGFR-ERK cascade.…”

Section: Role Of Cardiotonic Steroids In Renal Failurementioning

confidence: 99%

Endogenous digitalis: pathophysiologic roles and therapeutic applications

2008

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SUMMARYEndogenous digitalis-like factors, also called cardiotonic steroids, have been thought for nearly half a century to have important roles in health and disease. The endogenous cardiotonic steroids ouabain and marinobufagenin have been identified in humans, and an effector mechanism has been delineated by which these hormones signal through the sodium/potassium-transporting ATPase. These findings have increased interest in this field substantially. Although cardiotonic steroids were first considered important in the regulation of renal sodium transport and arterial pressure, subsequent work has implicated these hormones in the control of cell growth, apoptosis and fibrosis, among other processes. This Review focuses on the role of endogenous cardiotonic steroids in the pathophysiology of essential hypertension, congestive heart failure, end-stage renal disease and pre-eclampsia. We also discuss potential therapeutic strategies that have emerged as a result of the increased understanding of the regulation and actions of cardiotonic steroids.

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Section: Role Of Cardiotonic Steroids In Renal Failurementioning

confidence: 99%

Endogenous digitalis: pathophysiologic roles and therapeutic applications

2008

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“…On the other hand, MS/MS analysis of the authentic MBG showed specific daughter ions as described before. 16 The Y-1-derived TN. 37 fraction exhibited an MBT-specific daughter ion spectrum as shown in Figure 3A, and the TN 46 fraction showed an MBG-specific daughter ion spectrum as shown in Figure 3B.…”

Section: Structural Characterization Of Mbgi Elisa-positive Fractionsmentioning

confidence: 99%

“…16 Marinobufotoxin (MBT) was extracted from the skin of Bufo marinus and purified by preparative high-performance liquid chromatography (HPLC) and then by analytical HPLC. Finally, MBT in the 50% acetonitrile fraction of analytical HPLC was purified.…”

Section: Preparation Of Mbg and Marinobufotoxinmentioning

confidence: 99%

“…16 The column was equilibrated with 20% acetonitrile in H 2 O/0.01% trifluoroacetic acid at a flow rate of 0.5 mL/min and eluted with gradient elution over 90 minutes. The percentage of acetonitrile was raised to 35% at 20 minutes, 40% at 30 minutes, and 80% until 90 minutes in a linear mode and monitored by the ultraviolet absorbance at 230 nm.…”

Section: Hplc Analysis Of Supernatantmentioning

confidence: 99%

“…Very recently, we have identified telecinobufagin (TCB), a 2-hydrogen-added form of MBG, by liquid chromatography (LC)/mass spectrometry (MS), as well as MBG in the human plasma. 16 Thus, the recent understanding is that various kinds of cardenolides and bufadienolides exist in the mammalian biological fluids and tissues.…”

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confidence: 99%

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Novel Digitalis-Like Factor, Marinobufotoxin, Isolated From Cultured Y-1 Cells, and Its Hypertensive Effect in Rats

et al. 2007

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Abstract-Marinobufagenin and telecinobufagin have been identified as digitalis-like factors in mammals. In toads, marinobufagenin-related compounds, such as marinobufotoxin (MBT), have been isolated in some tissues but not in mammals, and its biological action has not been elucidated. Herein, we aimed to explore the possible production and/or secretion of MBT and the biological action in rats. First, the MBT in culture supernatant of the adrenocortical-originated cell line Y-1 was analyzed by high-performance liquid chromatography and sensitive ELISA for marinobufagenin-like immunoreactivity. Moreover, the structural information was obtained by mass spectrometry. To determine the biological action, MBT (9.6 and 0.96 g/kg per day) was intraperitoneally infused via an osmotic minipump for 1 week. Blood pressure and renal excretion of marinobufagenin-like immunoreactivity were measured. Marinobufagenin-like immunoreactivity was found in Y-1 cell culture media, and the concentration increased until 24 hours. The structural analysis suggested that marinobufagenin-like immunoreactivities were marinobufagenin and MBT, and tandem mass spectrum analysis revealed them with the specific daughter ions. The highest sensitive ELISA-positive peak of marinobufageninlike immunoreactivity in the media was MBT. Continuous administration of MBT in rats for 1 week significantly increased systolic blood pressure and renal excretion of marinobufagenin-like immunoreactivity compared with control rats (135Ϯ3.0 versus 126Ϯ2.0 mm Hg and 1.41Ϯ0.286 versus 0.34Ϯ0.064 ng/day, respectively). These data suggest that MBT, arginine-suberoyl ester of marinobufagenin, can be a novel digitalis-like factor with hypertensive action and is secreted from the adrenocortical cells.

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Regulation of renal function and structure by the signaling Na/K-ATPase

Xie

2013

IUBMB Life

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The Na/K-ATPase as an essential ion pump was discovered more than 50 years ago (1,2). The signaling function of Na/K-ATPase has been gradually appreciated over the last 20 years, first from the studies of regulatory effects of ouabain on cardiac cell growth. Several reviews on this topic have been written during the last few years (3–8). This article will focus on the molecular mechanism of Na/KATPase-mediated signal transduction and its potential regulatory role in renal physiology and diseases.

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A novel endogenous digitalis, telocinobufagin, exhibits elevated plasma levels in patients with terminal renal failure

Cited by 138 publications

References 35 publications

Endogenous digitalis: pathophysiologic roles and therapeutic applications

Endogenous digitalis: pathophysiologic roles and therapeutic applications

Novel Digitalis-Like Factor, Marinobufotoxin, Isolated From Cultured Y-1 Cells, and Its Hypertensive Effect in Rats

Regulation of renal function and structure by the signaling Na/K-ATPase

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