Regulation of Na,K-adenosine triphosphatase gene expression by sodium ions in cultured neonatal rat cardiocytes.

Yamamoto, Keiji; Ikeda, Uichi; Seino, Yoshitane; Tsuruya, Yoshio; Oguchi, Asahiko; Okada, Koji; Ishikawa, San‐e; Saito, Toshikazu; Kawakami, Kiyoshi; Hara, Yukichi

doi:10.1172/jci116781

Cited by 64 publications

(39 citation statements)

References 47 publications

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“…4-week-old SHR compared with that of WKY at the same age. Alterations in intracellular Na+ levels can induce a change in Na, K-ATPase gene expression, as in our previous study showing that Na+ induces a transient increase in the a and /3 isoform mRNA expression in cultured neonatal rat cardiocytes (36).…”

Section: Discussionsupporting

confidence: 68%

Altered Na, K-ATPase mRNA Expression in Spontaneously Hypertensive Rats.

Tsuruya¹,

Ikeda²,

Yamamoto³

et al. 1993

Hypertens Res

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We investigated the expression of Na, K-ATPase a and isoform mRNAs in spontaneously hypertensive rat (SHR) hearts, aortae and kidneys, compared with findings in normotensive Wistar-Kyoto rat (WKY), to obtain insight into the role of these isoforms in the development of hypertension in SHR. We used 4-, 8-, and 16-week-old SHR and WKY. Systolic blood pressure was recorded by tail sphygmomanometry. The expression of Na, K-ATPase a and fi isoform mRNAs was analyzed by Northern blot hybridization, using isoform specific cDNA probes. In the ventricles, pre-hypertensive 4-week-old SHR showed a significant 3 to 4-fold increase in the al and a2 isoform mRNA accumulation compared with age-matched WKY. The a3 isoform mRNA expression was detected only in 4-week-old SHR hearts. The pattern of flu mRNA expression resembled that of al or a2 mRNAs, and a significant 7-fold increase was observed in 4-week-old SHR compared with age-matched WKY. In the aortae, the a1 and a2 isoform mRNAs were expressed, and 4-week-old SHR exhibited a significant 5-fold increase in the al and a2 isoform mRNA levels compared with age-matched WKY. In the kidneys, only the al isoform mRNA was expressed, and that of SHR showed a significant 2-fold increase compared with age-matched WKY. We conclude that the expression of Na, K-ATPase a and 9 isoform mRNAs is significantly increased in the hearts, aortae and kidneys of SHR before the onset of hypertension. These findings suggest that, in this model, the altered expression of Na, K-ATPase gene is an early, if not a primary, event in the development of hypertension. (Hypertension Res 1993; 16: 269-274)

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Section: Discussionsupporting

confidence: 68%

Altered Na, K-ATPase mRNA Expression in Spontaneously Hypertensive Rats.

Tsuruya¹,

Ikeda²,

Yamamoto³

et al. 1993

Hypertens Res

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“…Although numerous studies performed in plants highlight the influence of intracellular sodium in triggering the expression of numerous genes, very little information has been obtained in animal cells, except for studies in which sodium has been shown to affect the expression of subunits of Na ϩ ,K ϩ -ATPase, a crucial enzyme responsible for cell sodium homeostasis (54). In cardiac myocytes, indirect evidence was obtained by using ouabain and digitalis at concentrations that increase [Na ϩ ] i (by inhibiting the Na ϩ ,K ϩ -ATPase activity) (53).…”

Section: Discussionmentioning

confidence: 99%

Increases in intracellular sodium activate transcription and gene expression via the salt-inducible kinase 1 network in an atrial myocyte cell line

Popov

Venetsanou

Chedrese

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Popov S, Venetsanou K, Chedrese PJ, Pinto V, Takemori H, Franco-Cereceda A, Eriksson P, Mochizuki N, Soares-da-Silva P, Bertorello AM. Increases in intracellular sodium activate transcription and gene expression via the salt-inducible kinase 1 network in an atrial myocyte cell line. Am J Physiol Heart Circ Physiol 303: H57-H65, 2012. First published March 30, 2012 doi:10.1152/ajpheart.00512.2011.-Cardiac hypertrophy (CH) generally occurs as the result of the sustained mechanical stress caused by elevated systemic arterial blood pressure (BP). However, in animal models, elevated salt intake is associated with CH even in the absence of significant increases in BP. We hypothesize that CH is not exclusively the consequence of mechanical stress but also of other factors associated with elevated BP such as abnormal cell sodium homeostasis. We examined the effect of small increases in intracellular sodium concentration ([Na ϩ ]i) on transcription factors and genes associated with CH in a cardiac cell line. Increases in [Na ϩ ]i led to a timedependent increase in the expression levels of mRNA for natriuretic peptide and myosin heavy chain genes and also increased myocyte enhancer factor (MEF)2/nuclear factor of activated T cell (NFAT) transcriptional activity. Increases in [Na ϩ ]i are associated with activation of salt-inducible kinase 1 (snflk-1, SIK1), a kinase known to be critical for cardiac development. Moreover, increases in [Na ϩ ]i resulted in increased SIK1 expression. Sodium did not increase MEF2/ NFAT activity or gene expression in cells expressing a SIK1 that lacked kinase activity. The mechanism by which SIK1 activated MEF2 involved phosphorylation of HDAC5. Increases in [Na ϩ ]i activate SIK1 and MEF2 via a parallel increase in intracellular calcium through the reverse mode of Na ϩ /Ca 2ϩ -exchanger and activation of CaMK1. These data obtained in a cardiac cell line suggest that increases in intracellular sodium could influence myocardial growth by controlling transcriptional activation and gene expression throughout the activation of the SIK1 network.hypertension; cardiac hypertrophy; Na ϩ ,K ϩ -ATPase; ion gradients CARDIAC HYPERTROPHY IS CONSIDERED to be the heart's response to sustained mechanical stress caused by either obstruction of cardiac outflow (valve stenosis) or elevated systemic arterial blood pressure. At the molecular level, its development involves the activation of numerous genes and transcription factors (9, 18, 30) that ultimately lead to abnormal myocardial growth. Hypertension is presently one of the major causes of cardiac hypertrophy. Although systemic hypertension has multiple causes, it ultimately results from the kidney's inability to maintain sodium homeostasis after normal or excessive sodium intake (1, 16). Whereas a sustained increase in systemic blood pressure is likely to influence the development of cardiac hypertrophy, it has also been demonstrated that high salt intake is associated with left ventricle hypertrophy even without significant increases in systemic blood pr...

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“…Experiments show that when mucosal glucose is increased and kept high, the increase in intracellular Na ϩ ([Na c ]) is followed by a slow decrease back to basal values, indicating a mechanism that increases the number of Na-K-ATPase transporter proteins to maintain Na ϩ homeostasis (30). This increase may stem from increased synthesis as it has been shown to do in central neurons and cardiocytes (74,98) or from a cytoplasmic holding area of available Na-K-ATPase proteins (73).…”

Section: Extending the Model To Test Regulatory Mechanismsmentioning

confidence: 99%

“…Intracellular Na ϩ has been shown to directly regulate the Na-K-ATPase gene expression in other cell types (74,98).…”

Section: Extending the Model To Test Regulatory Mechanismsmentioning

confidence: 99%

“…The intracellular Na ϩ activation of Na-K-ATPase synthesis has been shown for other cell types, where it increases the amount of mRNA coding for both the ␣-and ␤-subunits that combines into Na-K-ATPase (74, 98). Yamamoto et al (98) showed that this increase, in cardiocytes, was directly caused by Na ϩ due to Na ϩ -responsive sequences located within the 5=-flanking regions of the ␣-gene (␣ 1 -, ␣ 2 -, and ␣ 3 -isoforms). Parallels can be drawn to the intestinal enterocytes as they express the ␣ 1 -isoform (44).…”

Section: Regulatory Mechanisms and Namentioning

confidence: 99%

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Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model

Thorsen

Drengstig

Ruoff

2014

American Journal of Physiology-Cell Physiology

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Thorsen K, Drengstig T, Ruoff P. Transepithelial glucose transport and Na ϩ /K ϩ homeostasis in enterocytes: an integrative model. Am J Physiol Cell Physiol 307: C320 -C337, 2014. First published June 4, 2014; doi:10.1152/ajpcell.00068.2013.-The uptake of glucose and the nutrient coupled transcellular sodium traffic across epithelial cells in the small intestine has been an ongoing topic in physiological research for over half a century. Driving the uptake of nutrients like glucose, enterocytes must have regulatory mechanisms that respond to the considerable changes in the inflow of sodium during absorption. The Na-K-ATPase membrane protein plays a major role in this regulation. We propose the hypothesis that the amount of active Na-K-ATPase in enterocytes is directly regulated by the concentration of intracellular Na ϩ and that this regulation together with a regulation of basolateral K permeability by intracellular ATP gives the enterocyte the ability to maintain ionic Na ϩ /K ϩ homeostasis. To explore these regulatory mechanisms, we present a mathematical model of the sodium coupled uptake of glucose in epithelial enterocytes. Our model integrates knowledge about individual transporter proteins including apical SGLT1, basolateral Na-K-ATPase, and GLUT2, together with diffusion and membrane potentials. The intracellular concentrations of glucose, sodium, potassium, and chloride are modeled by nonlinear differential equations, and molecular flows are calculated based on experimental kinetic data from the literature, including substrate saturation, product inhibition, and modulation by membrane potential. Simulation results of the model without the addition of regulatory mechanisms fit well with published short-term observations, including cell depolarization and increased concentration of intracellular glucose and sodium during increased concentration of luminal glucose/sodium. Adding regulatory mechanisms for regulation of Na-K-ATPase and K permeability to the model show that our hypothesis predicts observed long-term ionic homeostasis.enterocytes; epithelial transport; homeostasis; mathematical modeling; ionic regulation THE UPTAKE AND TRANSPORT OF glucose by the epithelial enterocytes in the small intestine are essential steps in all higher animals. Much of the glucose uptake in the small intestine is coupled to transport of sodium, and the different transporter proteins involved in the sodium coupled glucose uptake are well known (23,61,67,97). Although the electrochemical kinetics of the individual transporter proteins responsible for glucose and nutrient uptake are fairly elucidated (19,54,67,82,97), the combined function in which these transporters drive a net inflow of nutrients from the intestinal lumen to the serosal blood has not yet been modeled in detail.We have developed a mathematical model of an enterocyte that incorporates the available kinetic data from studies on individual transporter proteins. The model includes apical SGLT1 (the glucose sodium cotransporter), coupled apical flow of Na ϩ an...

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Regulation of Na,K-adenosine triphosphatase gene expression by sodium ions in cultured neonatal rat cardiocytes.

Cited by 64 publications

References 47 publications

Altered Na, K-ATPase mRNA Expression in Spontaneously Hypertensive Rats.

Altered Na, K-ATPase mRNA Expression in Spontaneously Hypertensive Rats.

Increases in intracellular sodium activate transcription and gene expression via the salt-inducible kinase 1 network in an atrial myocyte cell line

Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model

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Regulation of Na,K-adenosine triphosphatase gene expression by sodium ions in cultured neonatal rat cardiocytes.

Cited by 64 publications

References 47 publications

Altered Na, K-ATPase mRNA Expression in Spontaneously Hypertensive Rats.

Altered Na, K-ATPase mRNA Expression in Spontaneously Hypertensive Rats.

Increases in intracellular sodium activate transcription and gene expression via the salt-inducible kinase 1 network in an atrial myocyte cell line

Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model

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Transepithelial glucose transport and Na⁺/K⁺ homeostasis in enterocytes: an integrative model