Na/K-ATPase Signaling and Salt Sensitivity: The Role of Oxidative Stress

Liu, Jiang; Yan, Yanling; Nie, Ying; Shapiro, Joseph I.

doi:10.3390/antiox6010018

Cited by 15 publications

(11 citation statements)

References 158 publications

(187 reference statements)

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“…Furthermore, MBG has been shown to regulate the permeability and gene expression of human brain microvascular endothelial cells in culture [31], increasing the interest in evaluating the possible role of MBG in cerebrovascular and other related vascular disease conditions. Recent studies have investigated the roles of MBG in angiogenic and stress signaling [32], modulation of oxidative stress [33] and neuroinflammation [11]. These findings support the earlier hypothesis that MBG activates endothelial NADPH oxidase [34].…”

Section: Discussionsupporting

confidence: 79%

“…The interaction of MBG at different concentrations with alpha 1 isoforms of the Na, K ATPase, its activation of the non-receptor tyrosine kinase Src by a sodium pump-evoked signal transduction and the activation of oxidant-sensitive enzymes also support the concept that MBG can induce endothelial oxidase stress. These findings contribute to the hypothesis that MBG may be a link between salt sensitivity, increased vascular mortality, and cardiovascular disease, including stroke [11,33,34].…”

Section: Discussionmentioning

confidence: 73%

See 1 more Smart Citation

Plasma Levels of the Cardiotonic Steroid Marinobufagenin in Ischemic Stroke Survivors and Treated Hypertensives: A Pilot Study

Estapé

González-Sepúlveda

Wei

et al. 2018

Int Arch Transl Med

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Background: Numerous studies have demonstrated a strong relationship between circulating levels of marinobufagenin (MBG) and salt-sensitivity. Since salt-sensitive hypertensives have increased plasma levels of MBG and are known to be at a higher risk of having cardiovascular events, stroke and increased mortality, we evaluated the possibility of an association between MBG and ischemic stroke. In this pilot study, we determined plasma MBG levels in patients after surviving an ischemic stroke compared to similar age and gender groups of treated hypertensives and normotensive controls. Methods: We measured plasma MBG levels in a total of 40 participants subdivided into three groups: After an ischemic stroke STR (n = 13), participants with a diagnosis of hypertension receiving blood pressure medication HT (n = 14) and normotensive control subjects CTL (n = 13). We used inferential statistics (parametric or non-parametric) and ordered logistic regression models (unadjusted and adjusted) and all statistical analyses were performed using Stata 14. Results: We did not include a subject from the CTL group because of a diagnosis of glucose-6-phosphate dehydrogenase deficiency and an extreme plasma MBG value of 2,246 pmol/L. Participants’ mean age was 60.4 ± 11.5 years; 56% were male. There was no significant difference between study groups (p > 0.05) for gender, age, and body mass index. HbA1c levels were significantly higher in the STR as compared to the CTL p < 0.05). In the STR group MBG levels were below the normal range (< 200 pmol/L) in three (23%), eight (61%) were in the normal range (200–400 pmol/L), while two (16%) had increased MBG values (> 400 pmol/L). Also, among the STR, the plasma MBG levels did not differ between those receiving and not receiving thrombolytic therapy (p > 0.05). From the 14 HT participants, six (43%) had MBG plasma levels within the normal range, and eight (57%) had high concentrations (> 400 pmol/L). Four (29%) of the treated hypertensives had extreme MBG levels (> 1,000 pmol/L) and normal values of blood pressure. Conclusion: There was no significant elevation of plasma MBG in survivors 24 h or more after an ischemic stroke. The extreme values of plasma MBG in 29% of the treated hypertensives suggests the presence of salt-sensitivity and a possible side effect of a specific combination of medications. Both of these findings contribute new knowledge to the design of studies to define if there is an MBG molecular mechanism underlying the complex associations among salt-sensitivity, hypertension, and ischemic stroke.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 73%

Plasma Levels of the Cardiotonic Steroid Marinobufagenin in Ischemic Stroke Survivors and Treated Hypertensives: A Pilot Study

Estapé

González-Sepúlveda

Wei

et al. 2018

Int Arch Transl Med

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“…Due to this, obese TH mice might be prone to developing hypertension when challenged with a high salt diet (Figure 3C and Figure 4B). In particular, Na/K-ATPase is highly sensitive to changes in the redox state [55,56,57]. The mechanisms of its redox sensitivity remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have reported the association of obesity with increased reabsorption of Na + in proximal tubules [59,60,61], impaired pressure natriuresis, and then hypertension [29]. Endogenous cardiotonic steroids (CTS) in humans and rodents [57,62], can signal through Na/K-ATPase, regulating renal salt handling in the proximal tubules [11,13,16] and contributing to salt-sensitive hypertension [12,15]. Since lithium (Li) is the marker for proximal tubular delivery [63], the data in this present study that correlates urinary total Na + and lithium excretion showed genuinely proportional excretion of both ions (Figure 2C), implicating identical handling of lithium and Na + in the proximal tubules in these two strains.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling

Yan

Wang

Chaudhry

et al. 2019

IJMS

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We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na+ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na+ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice.

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“…Sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) is an important membrane enzyme which plays a key role in cell structure and physiology by providing a sodium-potassium gradient in all cell membranes [20]. Tissue is the marker of viability during organ transplantation [20]. There is no study which adequately demonstrates the role of the Na+/K+-ATPase pump in the development of mesenteric I/R injury.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effect of Spironolactone and Role of the Na /K -ATPase Pump on Intestinal Ischemia/Reperfusion Injury

Akyüz¹,

Uzun²,

Sunamak³

et al. 2018

jrp

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The aim of this study was to evaluate the possible protective effect of spironolactone (SPL) and role of the Na-K ATPase pump on intestinal ischemia/reperfusion injury. In our study, the period of ischemia was established by clamping the mesenteric artery for 45 minunder anesthesia in Wistar albino rats and the animals left for reperfusion at the end of this period were decapitated after one hour. Spironolactone (20 mg kg-1) was administered orally for three days before ischemia, 30 minbefore ischemia. The control group rats were subjected to the Sham operation and administered saline solution. TNF-α and IL-1β levels were measured in the serum samples. Ileal Na+/K+-ATPase, myeloperoxidase (MPO) analysis were performed. Structural injury was assessed histopathologically. Ischemia/reperfusion increased serum TNF-α and IL-1β levels together with MPO activity, whereas these values were maintained at the control group levels through SPL activation. However, ischemia/reperfusion decreased Na+/K+-ATPase activity in ileal tissues; however, these parameters were found to be significantly increased with SPL activation. The protective effect of SPL against ischemia/reperfusion injury by different mechanisms, mainly the activity of the Na+/K+-ATPase pump, suggests that this nontoxic agent may constitute a new clinical therapeutic principle.

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Na/K-ATPase Signaling and Salt Sensitivity: The Role of Oxidative Stress

Cited by 15 publications

References 158 publications

Plasma Levels of the Cardiotonic Steroid Marinobufagenin in Ischemic Stroke Survivors and Treated Hypertensives: A Pilot Study

Plasma Levels of the Cardiotonic Steroid Marinobufagenin in Ischemic Stroke Survivors and Treated Hypertensives: A Pilot Study

Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling

The Protective Effect of Spironolactone and Role of the Na /K -ATPase Pump on Intestinal Ischemia/Reperfusion Injury

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