Salt loading induces redistribution of the plasmalemmal Na/K-ATPase in proximal tubule cells

Periyasamy, Sumudra; Liu, Jiang; Tanta, Feras; Kabak, Besher; Wakefield, Brent; Malhotra, Deepak; Kennedy, David J.; Nadoor, Alaa; Федорова, О. В.; Gunning, William T.; Xie, Zijian; Bagrov, Alexei Y.; Shapiro, Joseph I.

doi:10.1111/j.1523-1755.2005.00285.x

Cited by 72 publications

(95 citation statements)

References 43 publications

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“…We have demonstrated that activation of this Na/K-ATPase signaling function inhibits RPT sodium reabsorption to correct sodium retention-related volume expansion and blood pressure increase. We conclude that, rather than contributing to development and maintenance of hypertension, properly regulated RPT Na/K-ATPase signaling has a protective effect under physiological settings (12,13,21,22). However, a fundamental unanswered question is the underlying mechanism to "turn on/off" the RPT Na/K-ATPase signaling.…”

Section: Discussionmentioning

confidence: 82%

“…These include transgenic mice with a "humanized" ouabain-sensitive Na/K-ATPase ␣1 subunit, CTS infusion, and immunoneutralization of endogenous CTS (12,22,(37)(38)(39)(40). For many years, the concept of CTS elimination of excessive sodium by direct inhibition of Na/KATPase has been a topic of debate.…”

Section: Discussionmentioning

confidence: 99%

“…However, a fundamental unanswered question is the underlying mechanism to "turn on/off" the RPT Na/K-ATPase signaling. Marinobufagenin, another ligand of the Na/K-ATPase, stimulates ROS generation, protein oxidation, trafficking of RPT Na/K-ATPase, and urinary sodium excretion in experimental animals (12,40,41). The impaired RPT Na/K-ATPase⅐c-Src signaling in Dahl saltsensitive rats (22) prompted us to investigate the underlying mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of Reactive Oxygen Species in a Feed-forward Mechanism of Na/K-ATPase-mediated Signaling Transduction

Yan

Shapiro

Haller

et al. 2013

Journal of Biological Chemistry

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162

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Involvement of Reactive Oxygen Species in a Feed-forward Mechanism of Na/K-ATPase-mediated Signaling Transduction

Yan

Shapiro

Haller

et al. 2013

Journal of Biological Chemistry

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162

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“…20 Before sacrifice at 4 weeks, animals had ventricular pressures determined by placement of a 2F Millar Microtip Catheter Transducer (Millar Instruments Inc) into the left ventricle through a carotid insertion. Hemodynamic data were acquired at 500 Hz and stored electronically using a BioPac MP110 acquisition system and AcqKnowledge 4.7.3 software (BIOPAC Systems, Inc).…”

Section: Hemodynamicsmentioning

confidence: 99%

“…Recently, our group has shown that passive administration of antibodies raised against MBG reduced Na/K-ATPase endocytosis and sodium excretion in Sprague-Dawley rats given a high-salt diet. 20 On this background, we postulated that increases in circulating MBG may be in part responsible for the systemic oxidant stress state and the anatomic and functional cardiac changes seen with experimental uremia.…”

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confidence: 99%

Central Role for the Cardiotonic Steroid Marinobufagenin in the Pathogenesis of Experimental Uremic Cardiomyopathy

et al. 2006

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Abstract-Patients with chronic renal failure develop a "uremic" cardiomyopathy characterized by diastolic dysfunction, cardiac hypertrophy, and systemic oxidant stress. Patients with chronic renal failure are also known to have increases in the circulating concentrations of the cardiotonic steroid marinobufagenin (MBG). On this background, we hypothesized that elevations in circulating MBG may be involved in the cardiomyopathy. First, we observed that administration of MBG (10 g/kg per day) for 4 weeks caused comparable increases in plasma MBG as partial nephrectomy at 4 weeks. MBG infusion caused increases in conscious blood pressure, cardiac weight, and the time constant for left ventricular relaxation similar to partial nephrectomy. Decreases in the expression of the cardiac sarcoplasmic reticulum ATPase, cardiac fibrosis, and systemic oxidant stress were observed with both MBG infusion and partial nephrectomy. Next, rats were actively immunized against a MBG-BSA conjugate or BSA control, and partial nephrectomy was subsequently performed. Immunization against MBG attenuated the cardiac hypertrophy, impairment of diastolic function, cardiac fibrosis, and systemic oxidant stress seen with partial nephrectomy without a significant effect on conscious blood pressure. These data suggest that the increased concentrations of MBG are important in the cardiac disease and oxidant stress state seen with renal failure.

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Proximal Nephron

Zhuo,

2013

Comprehensive Physiology

174

140

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The kidney plays a fundamental role in maintaining body salt and fluid balance and blood pressure homeostasis through the actions of its proximal and distal tubular segments of nephrons. However, proximal tubules are well recognized to exert a more prominent role than distal counterparts. Proximal tubules are responsible for reabsorbing approximately 65% of filtered load and most, if not all, of filtered amino acids, glucose, solutes, and low molecular weight proteins. Proximal tubules also play a key role in regulating acid-base balance by reabsorbing approximately 80% of filtered bicarbonate. The purpose of this review article is to provide a comprehensive overview of new insights and perspectives into current understanding of proximal tubules of nephrons, with an emphasis on the ultrastructure, molecular biology, cellular and integrative physiology, and the underlying signaling transduction mechanisms. The review is divided into three closely related sections. The first section focuses on the classification of nephrons and recent perspectives on the potential role of nephron numbers in human health and diseases. The second section reviews recent research on the structural and biochemical basis of proximal tubular function. The final section provides a comprehensive overview of new insights and perspectives in the physiological regulation of proximal tubular transport by vasoactive hormones. In the latter section, attention is particularly paid to new insights and perspectives learnt from recent cloning of transporters, development of transgenic animals with knockout or knockin of a particular gene of interest, and mapping of signaling pathways using microarrays and/or physiological proteomic approaches.

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Salt loading induces redistribution of the plasmalemmal Na/K-ATPase in proximal tubule cells

Abstract: These data suggest that redistribution of the proximal tubule Na/K-ATPase in response to endogenous cardiotonic steroids plays an important role in renal adaptation to salt loading.

Cited by 72 publications

References 43 publications

Involvement of Reactive Oxygen Species in a Feed-forward Mechanism of Na/K-ATPase-mediated Signaling Transduction

Involvement of Reactive Oxygen Species in a Feed-forward Mechanism of Na/K-ATPase-mediated Signaling Transduction

Central Role for the Cardiotonic Steroid Marinobufagenin in the Pathogenesis of Experimental Uremic Cardiomyopathy

Proximal Nephron

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