Radioimmunoassay of plasma ouabain in healthy and pregnant individuals

Vakkuri, Olli; Árnason, Sighvatur S.; Pouta, Anneli; Vuolteenaho, Olli; Leppäluoto, Juhani

doi:10.1677/joe.0.1650669

Cited by 35 publications

(27 citation statements)

References 38 publications

(50 reference statements)

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“…In agreement with previous studies, 15,21 we found higher levels of circulating ouabain in pregnant women ( Figure 10A). However, no significant differences in the steroid concentration were found at the different times tested.…”

Section: Abundance Of Circulating Ouabain In Human Fetal and Maternalsupporting

confidence: 93%

Reduction in Maternal Circulating Ouabain Impairs Offspring Growth and Kidney Development

Dvela‐Levitt¹,

Ami²,

Rosen³

et al. 2015

Journal of the American Society of Nephrology

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Ouabain, a steroid present in the circulation and in various tissues, was shown to affect the growth and viability of various cells in culture. To test for the possible influence of this steroid on growth and viability in vivo, we investigated the involvement of maternal circulating ouabain in the regulation of fetal growth and organ development. We show that intraperitoneal administration of anti-ouabain antibodies to pregnant mice resulted in a .80% decline in the circulating ouabain level. This reduction caused a significant decrease in offspring body weight, accompanied by enlargement of the offspring heart and inhibition of kidney and liver growth. Kidney growth inhibition was manifested by a decrease in the size and number of nephrons. After the reduction in maternal circulating ouabain, kidney expression of cyclin D1 was reduced and the expression of the a1 isoform of the Na + , K + -ATPase was increased. In addition, the elevation of proliferation signals including ERK1/2, p-90RSK, Akt, PCNA, and Ki-67, and a reduction in apoptotic factors such as Bax, caspase-3, and TUNEL were detected. During human pregnancy, the circulating maternal ouabain level increased and the highest concentration of the steroid was found in the placenta. Furthermore, circulating ouabain levels in women with small-for-gestational age neonates were significantly lower than the levels in women with normal-for-gestational age newborns. These results support the notion that ouabain is a growth factor and suggest that a reduction in the concentration of this hormone during pregnancy may increase the risk of impaired growth and kidney development.

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Section: Abundance Of Circulating Ouabain In Human Fetal and Maternalsupporting

confidence: 93%

Reduction in Maternal Circulating Ouabain Impairs Offspring Growth and Kidney Development

Dvela‐Levitt¹,

Ami²,

Rosen³

et al. 2015

Journal of the American Society of Nephrology

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“…29 In our study, the average level of plasma EO was 14.7±5.7 pmol l -1 , nevertheless our patients were treated with RAAS blockers and/or b-blockers. In our study, the levels of EO were lower than in some studies in literature using other immunoassay methods (enzyme-linked immunosorbent assay, EIA), which are, however, not comparable with our results because of the use of different antibody and methods.…”

Section: Discussionmentioning

confidence: 56%

Selective association of endogenous ouabain with subclinical organ damage in treated hypertensive patients

et al. 2010

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According to previous studies endogenous ouabain (EO) closely correlates with high blood pressure, congestive heart failure and kidney disease in humans. Our aims were to analyse associations between plasma, urinary EO level and various markers of cardiovascular damage in treated hypertensive patients. Forty-one adult patients with hypertension and/or diabetes mellitus (DM) and/or chronic kidney disease (CKD) were studied. We assessed plasma and urinary EO, pro-brain natriuretic peptide and catecholamines, profile of ambulatory blood pressure monitor and cardiovascular status by echocardiography and echo-tracking. The highest level of plasma EO (19.7 ± 9.5 pmol l -1 ) was measured in hypertensive patients with DM and CKD. The nighttime mean arterial blood pressure independently correlated with the level of plasma EO (P ¼ 0.004), while independent predictor of the b-stiffness of carotid artery was the urinary EO (P ¼ 0.011). Elevated level of EO was associated with nighttime blood pressure and subclinical organ damage in treated hypertensive patients, suggesting possible role of EO in the pathogenesis of impaired diurnal blood pressure rhythm and arterial stiffness.

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“…There now is strong evidence indicating that ouabain is a mammalian hormone that, like other steroid hormones, is synthesized and released from the adrenal gland (16,17,41). Circulating levels of ouabain in mammals is estimated to be in the picomolar range and has been reported to be significantly increased in conditions in which extensive cell growth and differentiation are required, including pregnancy (42), early postnatal life (43), and after unilateral nephrectomy (44), a condition that is associated with compensatory growth of the remaining kidney.…”

Section: Discussionmentioning

confidence: 99%

Low Doses of Ouabain Protect from Serum Deprivation–Triggered Apoptosis and Stimulate Kidney Cell Proliferation via Activation of NF-κB

Li¹,

Zelenin²,

Aperia³

et al. 2006

Journal of the American Society of Nephrology

122

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It now generally is agreed that Na,K-ATPase, in addition to its role in the maintenance of Na ؉ and K ؉ gradients across the cell membrane, plays a role in communicating information from the extracellular environment to intracellular signaling pathways. It was reported recently that interaction between ouabain-bound Na,K-ATPase and the 1,4,5-trisphosphate receptor (IP 3 R) triggers slow calcium oscillations and activation of NF-B. Here it is demonstrated that this signaling pathway can serve to prevent cell death and promote cell growth. Rat renal proximal tubular cells in primary culture first were grown in the presence of 10% serum and then exposed to 0.2% serum for 24 h to induce apoptosis. Serum starvation increased the apoptotic index from 1.21 ؎ 0.26 to 14.01 ؎ 1.17%. Ouabain in concentrations that did not inhibit Na,K-ATPase activity (1 to 10 nM) completely abolished the apoptotic effect of serum starvation. Ouabain protection from apoptosis was not observed when release of calcium from intracellular stores via the IP 3 R was prevented. It was shown that the NH 2 terminal tail of the Na,K-ATPase ␣ subunit plays a key role in ouabain-triggered calcium oscillations. It was found that ouabain did not protect from apoptosis in serum-deprived cells that expressed a mutant Na,K-ATPase ␣ subunit with deletion of the NH 2 terminal tail. . Recent studies suggest that Na,K-ATPase, in addition to being the major determinant of intracellular ion composition, may act as a signal transducer (2-5).Ouabain, a steroid derivative, is a specific ligand of Na,KATPase that dose-dependently inhibits the activity of Na,KATPase (6). Noninhibitory doses of ouabain activate the signaling function of Na,K-ATPase. The signaling cascade that is triggered by Na,K-ATPase is complex, and several different pathways have been implicated (7-9). We recently reported that ouabain can trigger an interaction between Na,K-ATPase and the inositol 1,4,5-trisphosphate (IP 3 ) receptor, which results in low-frequency Ca 2ϩ oscillations and activation of the transcription factor NF-B. This phenomenon was observed in rat renal proximal tubular cells in primary culture and in a kidney cell line (10).A number of recent studies have demonstrated that ouabain in noninhibitory doses can promote cell proliferation (11-13). Because NF-B has an antiapoptotic effect (14), we speculated that ouabain also might act to protect from apoptosis. Here we demonstrate that noninhibitory doses of ouabain can protect rat renal proximal tubular cells from serum deprivation-triggered apoptosis, albeit not from pharmacologically staurosporinetriggered apoptosis. We show that protection from serum-triggered apoptosis depends on NF-B activation. Normal kidney development is critically dependent on a well-controlled balance between cell proliferation and apoptosis (15). Accumulating evidence suggests that ouabain is a mammalian hormone, produced in the adrenal glands and the hypothalamus (16,17). Therefore, ouabain might play an important role as a modulator of kidney growth ...

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Radioimmunoassay of plasma ouabain in healthy and pregnant individuals

Cited by 35 publications

References 38 publications

Reduction in Maternal Circulating Ouabain Impairs Offspring Growth and Kidney Development

Reduction in Maternal Circulating Ouabain Impairs Offspring Growth and Kidney Development

Selective association of endogenous ouabain with subclinical organ damage in treated hypertensive patients

Low Doses of Ouabain Protect from Serum Deprivation–Triggered Apoptosis and Stimulate Kidney Cell Proliferation via Activation of NF-κB

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