Endogenous plasma Na,K-ATPase inhibitory activity and digoxin like immunoreactivity after acute myocardial infarction

Bagrov, Alexei Y.; Федорова, О. В.; Маслова, М. Н.; Roukoyatkina, Natalia I.; Ukhanova, Maria V.; Zhabko, E. P.

doi:10.1093/cvr/25.5.371

Cited by 44 publications

(25 citation statements)

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“…Hamlyn et al (1) demonstrated that there is a substance in plasma that cannot yet be distinguished from ouabain, even by electrospray ionization-mass spectrometry, 1 H-NMR, and liquid chromatography (2)(3)(4). Furthermore, the observation that this endogenous ouabain and its analogs increase during exercise (5), salty meals (6), and pathological conditions [such as arterial hypertension, eclampsia (7), and myocardial infarction (8)] raised the possibility that it may function as a hormone (9). This theory prompted efforts to unravel its physiological role (10).…”

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confidence: 99%

Ouabain modulates ciliogenesis in epithelial cells

Larre¹,

Castillo²,

Flores-Maldonado³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The exchange of substances between higher organisms and the environment occurs across transporting epithelia whose basic features are tight junctions (TJs) that seal the intercellular space, and polarity, which enables cells to transport substances vectorially. In a previous study, we demonstrated that 10 nM ouabain modulates TJs, and we now show that it controls polarity as well. We gauge polarity through the development of a cilium at the apical domain of Madin-Darby canine kidney cells (MDCK, epithelial dog kidney). Ouabain accelerates ciliogenesis in an ERK1/2-dependent manner. Claudin-2, a molecule responsible for the Na + and H 2 O permeability of the TJs, is also present at the cilium, as it colocalizes and coprecipitates with acetylated α-tubulin. Ouabain modulates claudin-2 localization at the cilium through ERK1/2. Comparing wild-type and ouabain-resistant MDCK cells, we show that ouabain acts through Na + ,K + -ATPase. Taken together, our previous and present results support the possibility that ouabain constitutes a hormone that modulates the transporting epithelial phenotype, thereby playing a crucial role in metazoan life.E-cadherin | occludin | cell adhesion | cardiotonic steroids

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confidence: 99%

Ouabain modulates ciliogenesis in epithelial cells

Larre¹,

Castillo²,

Flores-Maldonado³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Although several studies have shown a correlation between elevated endogenous cardiac glycosides and certain pathological conditions, the physiological function of endogenous cardiac glycoside-like compounds is still uncertain (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Plasma levels of endogenous cardiac glycosides are high in several animal models of hypertension, as well as in human essential hypertension and preeclampsia (10)(11)(12)(13)(14)(15)(16)(17).…”

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confidence: 99%

“…Plasma levels of endogenous cardiac glycosides are high in several animal models of hypertension, as well as in human essential hypertension and preeclampsia (10)(11)(12)(13)(14)(15)(16)(17). In addition, marked increases in endogenous ouabain-like compounds occur in congestive heart failure, both in animal models and human patients (18)(19)(20). One concern raised with respect to endogenous cardiac glycoside-like compounds is that they occur in levels which may not significantly inhibit the Na,K-ATPase.…”

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confidence: 99%

The highly conserved cardiac glycoside binding site of Na,K-ATPase plays a role in blood pressure regulation

Dostanic-Larson

Huysse

Lorenz

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

175

190

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The Na,K-ATPase contains a binding site for cardiac glycosides, such as ouabain, digoxin, and digitoxin, which is highly conserved among species ranging from Drosophila to humans. Although advantage has been taken of this site to treat congestive heart failure with drugs such as digoxin, it is unknown whether this site has a natural function in vivo. Here we show that this site plays an important role in the regulation of blood pressure, and it specifically mediates adrenocorticotropic hormone (ACTH)-induced hypertension in mice. We used genetically engineered mice in which the Na,K-ATPase ␣2 isoform, which is normally sensitive to cardiac glycosides, was made resistant to these compounds. Chronic administration of ACTH caused hypertension in WT mice but not in mice with an ouabain-resistant ␣2 isoform of Na,K-ATPase. This finding demonstrates that the cardiac glycoside binding site of the Na,K-ATPase plays an important role in blood pressure regulation, most likely by responding to a naturally occurring ligand. Because the ␣1 isoform is sensitive to cardiac glycosides in humans, we developed mice in which the naturally occurring ouabain-resistant ␣1 isoform was made ouabain-sensitive. Mice with the ouabainsensitive ''human-like'' ␣1 isoform and an ouabain-resistant ␣2 isoform developed ACTH-induced hypertension to greater extent than WT animals. This result indicates that the cardiac glycoside binding site of the ␣1 isoform can also mediate ACTH-induced hypertension. Taken together these results demonstrate that the cardiac glycoside binding site of the ␣ isoforms of the Na,K-ATPase have a physiological function and supports the hypothesis for a role of the endogenous cardiac glycosides. adrenocorticotropic hormone ͉ hypertension ͉ endogenous cardiac glycosides

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“…The identification of cardiac glycoside-like molecules in mammals has led to the proposal that these compounds are natural regulators of Na,K-ATPase in vivo (7)(8)(9)(10). Several studies have shown a correlation between these cardiac glycoside-like molecules and certain pathological conditions, such as hypertension and heart failure (11)(12)(13)(14)(15)(16)(17). Plasma levels of these putative ligands for the Na,KATPase are high in several animal hypertension models, as well as in human essential hypertension and preeclampsia (11-14, 18, 19).…”

mentioning

confidence: 99%

“…Plasma levels of these putative ligands for the Na,KATPase are high in several animal hypertension models, as well as in human essential hypertension and preeclampsia (11-14, 18, 19). In addition, marked increases in peripheral and central endogenous ouabain-like compounds occur in animal models of congestive heart failure as well as in human patients (15)(16)(17). However, it is still difficult to draw definitive conclusions regarding the specific function of these molecules in pathophysiology.…”

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confidence: 99%

The sodium pump and hypertension: A physiological role for the cardiac glycoside binding site of the Na,K-ATPase

Kaplan

2005

Proc. Natl. Acad. Sci. U.S.A.

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Endogenous plasma Na,K-ATPase inhibitory activity and digoxin like immunoreactivity after acute myocardial infarction

Abstract: The results show that plasma factor(s) with some of the properties of digitalis are increased in acute myocardial infarction.

Cited by 44 publications

References 0 publications

Ouabain modulates ciliogenesis in epithelial cells

Ouabain modulates ciliogenesis in epithelial cells

The highly conserved cardiac glycoside binding site of Na,K-ATPase plays a role in blood pressure regulation

The sodium pump and hypertension: A physiological role for the cardiac glycoside binding site of the Na,K-ATPase

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