Oleic and linoleic acids are active principles in Nigella sativa and stabilize an E2P conformation of the Na,K-ATPase. Fatty acids differentially regulate cardiac glycoside interaction with the pump

Yasser Ahmed Mahmmoud; Søren Brøgger Christensen

doi:10.1016/j.bbamem.2011.06.025

Oleic and linoleic acids are active principles in Nigella sativa and stabilize an E₂P conformation of the Na,K-ATPase. Fatty acids differentially regulate cardiac glycoside interaction with the pump

Yasser Ahmed Mahmmoud, Søren Brøgger Christensen

13 Citations (Scopus)

Abstract

Nigella sativa seed oil was found to contain a modulator of Na,K-ATPase. Separation analyses combined with ¹H NMR and GCMS identified the inhibitory fraction as a mixture of oleic and linoleic acids. These two fatty acids are specifically concentrated in several medicinal plant oils, and have particularly been implicated in decreasing high blood pressure. The ouabain binding site on Na,K-ATPase has also been implicated in blood pressure regulation. Thus, we aimed to determine how these two molecules modify pig kidney Na,K-ATPase. Oleic and linoleic acids did not modify reactions involving the E₁ (Na⁺) conformations of the Na,K-ATPase. In contrast, K⁺ dependent reactions were strongly modified after treatment. Oleic and linoleic acids were found to stabilize a pump conformation that binds ouabain with high affinity, i.e., an ion free E₂P form. Time-resolved binding assays using anthroylouabain, a fluorescent ouabain analog, revealed that the increased ouabain affinity is unique to oleic and linoleic acids, as compared with γ-linolenic acid, which decreased pump-mediated ATP hydrolysis but did not equally increase ouabain interaction with the pump. Thus, the dynamic changes in plasma levels of oleic and linoleic acids are important in the modulation of the sensitivity of the sodium pump to cardiac glycosides. Given the possible involvement of the cardiac glycoside binding site on Na,K-ATPase in the regulation of hypertension, we suggest oleic acid to be a specific chaperon that modulates interaction of cardiac glycosides with the sodium pump.

Original language	English
Journal	BBA General Subjects
Volume	1808
Issue number	10
Pages (from-to)	2413-2420
ISSN	0304-4165
DOIs	https://doi.org/10.1016/j.bbamem.2011.06.025
Publication status	Published - Oct 2011

Keywords

Former Faculty of Pharmaceutical Sciences

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10.1016/j.bbamem.2011.06.025

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Oleic and linoleic acids are active principles in Nigella sativa and stabilize an E₂P conformation of the Na,K-ATPase. Fatty acids differentially regulate cardiac glycoside interaction with the pump. / Mahmmoud, Yasser Ahmed; Christensen, Søren Brøgger.
In: BBA General Subjects, Vol. 1808, No. 10, 10.2011, p. 2413-2420.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "Oleic and linoleic acids are active principles in Nigella sativa and stabilize an E2P conformation of the Na,K-ATPase. Fatty acids differentially regulate cardiac glycoside interaction with the pump",

abstract = "Nigella sativa seed oil was found to contain a modulator of Na,K-ATPase. Separation analyses combined with 1H NMR and GCMS identified the inhibitory fraction as a mixture of oleic and linoleic acids. These two fatty acids are specifically concentrated in several medicinal plant oils, and have particularly been implicated in decreasing high blood pressure. The ouabain binding site on Na,K-ATPase has also been implicated in blood pressure regulation. Thus, we aimed to determine how these two molecules modify pig kidney Na,K-ATPase. Oleic and linoleic acids did not modify reactions involving the E1 (Na+) conformations of the Na,K-ATPase. In contrast, K+ dependent reactions were strongly modified after treatment. Oleic and linoleic acids were found to stabilize a pump conformation that binds ouabain with high affinity, i.e., an ion free E2P form. Time-resolved binding assays using anthroylouabain, a fluorescent ouabain analog, revealed that the increased ouabain affinity is unique to oleic and linoleic acids, as compared with γ-linolenic acid, which decreased pump-mediated ATP hydrolysis but did not equally increase ouabain interaction with the pump. Thus, the dynamic changes in plasma levels of oleic and linoleic acids are important in the modulation of the sensitivity of the sodium pump to cardiac glycosides. Given the possible involvement of the cardiac glycoside binding site on Na,K-ATPase in the regulation of hypertension, we suggest oleic acid to be a specific chaperon that modulates interaction of cardiac glycosides with the sodium pump.",

keywords = "Former Faculty of Pharmaceutical Sciences",

author = "Mahmmoud, {Yasser Ahmed} and Christensen, {S{\o}ren Br{\o}gger}",

note = "Keywords: Na,K-ATPase; Nigella Sativa; Oleic acid; Linoleic acid; Ouabain affinity; Anthroyl ouabain",

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AU - Mahmmoud, Yasser Ahmed

AU - Christensen, Søren Brøgger

N1 - Keywords: Na,K-ATPase; Nigella Sativa; Oleic acid; Linoleic acid; Ouabain affinity; Anthroyl ouabain

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N2 - Nigella sativa seed oil was found to contain a modulator of Na,K-ATPase. Separation analyses combined with 1H NMR and GCMS identified the inhibitory fraction as a mixture of oleic and linoleic acids. These two fatty acids are specifically concentrated in several medicinal plant oils, and have particularly been implicated in decreasing high blood pressure. The ouabain binding site on Na,K-ATPase has also been implicated in blood pressure regulation. Thus, we aimed to determine how these two molecules modify pig kidney Na,K-ATPase. Oleic and linoleic acids did not modify reactions involving the E1 (Na+) conformations of the Na,K-ATPase. In contrast, K+ dependent reactions were strongly modified after treatment. Oleic and linoleic acids were found to stabilize a pump conformation that binds ouabain with high affinity, i.e., an ion free E2P form. Time-resolved binding assays using anthroylouabain, a fluorescent ouabain analog, revealed that the increased ouabain affinity is unique to oleic and linoleic acids, as compared with γ-linolenic acid, which decreased pump-mediated ATP hydrolysis but did not equally increase ouabain interaction with the pump. Thus, the dynamic changes in plasma levels of oleic and linoleic acids are important in the modulation of the sensitivity of the sodium pump to cardiac glycosides. Given the possible involvement of the cardiac glycoside binding site on Na,K-ATPase in the regulation of hypertension, we suggest oleic acid to be a specific chaperon that modulates interaction of cardiac glycosides with the sodium pump.

AB - Nigella sativa seed oil was found to contain a modulator of Na,K-ATPase. Separation analyses combined with 1H NMR and GCMS identified the inhibitory fraction as a mixture of oleic and linoleic acids. These two fatty acids are specifically concentrated in several medicinal plant oils, and have particularly been implicated in decreasing high blood pressure. The ouabain binding site on Na,K-ATPase has also been implicated in blood pressure regulation. Thus, we aimed to determine how these two molecules modify pig kidney Na,K-ATPase. Oleic and linoleic acids did not modify reactions involving the E1 (Na+) conformations of the Na,K-ATPase. In contrast, K+ dependent reactions were strongly modified after treatment. Oleic and linoleic acids were found to stabilize a pump conformation that binds ouabain with high affinity, i.e., an ion free E2P form. Time-resolved binding assays using anthroylouabain, a fluorescent ouabain analog, revealed that the increased ouabain affinity is unique to oleic and linoleic acids, as compared with γ-linolenic acid, which decreased pump-mediated ATP hydrolysis but did not equally increase ouabain interaction with the pump. Thus, the dynamic changes in plasma levels of oleic and linoleic acids are important in the modulation of the sensitivity of the sodium pump to cardiac glycosides. Given the possible involvement of the cardiac glycoside binding site on Na,K-ATPase in the regulation of hypertension, we suggest oleic acid to be a specific chaperon that modulates interaction of cardiac glycosides with the sodium pump.

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