Endogenous ouabain regulates cell viability

Dvela, Moran; Rosen, Haim; Ben-Ami, Hagit Cohen; Lichtstein, David

doi:10.1152/ajpcell.00336.2011

Cited by 64 publications

(74 citation statements)

References 57 publications

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“…13 This effect was now tested on primary human fibroblasts, bovine aortic endothelial cells, and rat smooth muscle cells. The endogenous ouabain present at 0.5 nM in the media was reduced by 87% by treating the culture media with specific anti-ouabain antibodies.…”

Section: Reduction Of Endogenous Ouabain In the Culture Medium Inhibimentioning

confidence: 99%

“…11,12 We previously found that lowering the endogenous ouabain present in serum-supplemented tissue culture media, by treating the media with specific anti-ouabain antibodies, reduced the viability and growth of several cultured cell lines. 13 This suggested that ouabain serves as a growth factor, a notion that was recently addressed in relation to kidney growth and development. Studies by Li et al showed that the addition of exogenous ouabain to pregnant rats rescues the development of embryonic kidneys in animals given a low-protein diet, suggesting the steroid's role in kidney development.…”

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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: Reduction Of Endogenous Ouabain In the Culture Medium Inhibimentioning

confidence: 99%

mentioning

confidence: 99%

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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“…Essas enzimas têm suas atividades reguladas por fatores que podem promover o remodelamento vascular devido a uma maior degradação da matriz extracelular e permitinr a migração e proliferação de células musculares lisas e de células inflamatórias para a parede DMITRIEVA; DORIS, 2003;DVELA et al, 2012; KHUNDMIRI et a.l, 2007; KOMETIANI et al, 1998; KOTOVA et al, 2006; KULIKOV et al, 2007;LIU et al, 2000;MONTERO et al, 1993;MURATA et al, 1996;TREVISI et al, 2006;CAI, 2003;XU et al, 2009). Essa substância endógena vem sendo muito estudada quanto aos mecanismos que descrevem sua abilidade de alterar a reatividade vascular em ratos…”

Section: Figura 1 -Classificação De Artérias Quanto Ao Tipo De Remodeunclassified

Section: A Na + K + Atpase E a Ouabaínaunclassified

“…Além disso, esse gradiente eletroquímico transmembrana também é importante em processos como a contração muscular e a propagação do potencial de ação (LINGEL, 1992 DMITRIEVA;DORIS, 2003;DVELA et al, 2012; KHUNDMIRI et al, 2007; KOTOVA et al, 2006; KULIKOV et al, 2007;MONTERO et al, 1993;MURATA et al, 1996;TREVISI et al, 2006;XU et al, 2009 Hoje sabe-se que a OUA é produzida no hipotálamo, na região anteroventral do terceiro ventrículo (AV3V) e na zona glomerulosa e fasciculada do córtex da glândula adrenal, sendo a produção da região glomerulosa 5,5 vezes maior que a produção da região fasciculada (LAREDO; HAMILTON; HAMLYN, 1995;MASUGI et al, 1988). Sua síntese ocorre em resposta a estímulos como: o aumento de volume, a angiotensina II e/ou por estimulação do hormônio adrenocorticotrófico (BAGROV; SHAPIRO, 2008;BLAUSTEIN et al, 2009;GÓMEZ-SANCHEZ et al, 1994;LAREDO; HAMILTON; HAMLYN, 1994 HAMLYN, , 1995MATHWES et al, 1991; SCHEINER-BOBIS, 2007).…”

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Estudo dos mecanismos envolvidos no remodelamento de artérias de resistência de ratos hipertensos induzidos pelo tratamento com ouabaína.

Neto¹,

de²

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Estudo dos mecanismos envolvidos no remodelamento de artérias de resistência de ratos hipertensos induzidos pelo tratamento com ouabaínaTese apresentada ao Programa de Pós-Graduação em Fisiologia Humana USP/ Instituto de Ciências Biomédicas/ ICB, para obtenção do Título de Doutor em Fisiologia Humana. mg/kg/dia; v.o.; grupo HH). O grupo OUA apresentou elevação dos valores de pressão arterial e, ambos os co-tratamentos preveniram a resposta pressórica da OUA. As AMR dos ratos OUA apresentaram redução do diâmetro interno (Di), da área de secção transversa e do número de núcleos e aumento na rigidez, na quantidade de colágeno total e espécies reativas de oxigênio, as quais foram bloqueadas por todos co-ttos, exceto pela HH. Em AMR de ratos OUA, o SRA e a COX-2 participam da resposta pressórica, do remodelamento hipotrófico para dentro e da rigidez. Esses ajustes estão associados ao stress oxidativo e a deposição de colágeno na parede vascular estimulados pela capacidade da OUA em promover a ativação do receptor AT1 e da COX-2. The chronic administration of ouabain (OUA) induces hypertension in rats, functional and structural alterations in mesenteric resistance arteries (MRA). It is well known that OUA-induced hypertension is blocked by AT1 receptor antagonism and the COX-2 inhibition. However, the participation of these pathways in MRA remodeling in this model of hypertension remains unknown. This study aimed to investigate the role of the renin angiotensin system (RAS) and COX pathways on MRA remodeling induced by OUA. Male Wistar rats (45 days) were treated for 5 weeks with OUA (30 µg/kg/day, s.c.) and co-treated with losartan potassium (15 mg/kg/day, p.o.), aspirin (100 mg/kg/day; p.o.), nimesulide (20 mg/kg /day, p.o.) or hydralazine hydrochloride (44 mg/kg/day) plus hydrochlorothiazide (9.4 mg/kg/day; p.o.; HH group). The OUA group showed high blood pressure and both co-treatments prevented the pressor response of OUA. MRA of OUA rats showed reduced inner diameter and cross sectional area and increased arterial stiffness, the amount of total collagen and reactive oxygen species in the vascular wall, which were blocked by all co-treatments except for HH. In AMR from OUA rats, RAS and COX-2 participate in the pressor response, the inward hypotrophic remodeling and stiffness. These adjustments are the result of oxidative stressand increasing collagen deposition in the vascular wall stimulated by the OUA ability to stimulate the activation of AT1 receptor and COX-2.Keyworlds: Vascular remodeling. Ouabain. Arterial hypertension. Quanto à sua origem, a HA pode ser classificada como HA primária ou secundária. A HA primária é a forma de maior prevalência na população (90%). Essa forma da HA não possui causas definidas, mas está associada a muitos fatores de risco, como fatores hereditários, uma dieta pouco saudável, sedentarismo, stress ou abuso de bebidas alcoólicas. Por sua vez, a HA secundária tem prevalência de 3 a 5% e está associada à alguma condição clínica, como hiperaldosteronismo primário, feocromocitoma e ...

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Ouabain‐induced changes in MAP kinase phosphorylation in primary culture of rat cerebellar cells

Лопачев

Lopacheva

Osipova

et al. 2016

Cell Biochemistry & Function

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Cardiotonic steroid (CTS) ouabain is a well-established inhibitor of Na,K-ATPase capable of inducing signalling processes including changes in the activity of the mitogen activated protein kinases (MAPK) in various cell types. With increasing evidence of endogenous CTS in the blood and cerebrospinal fluid, it is of particular interest to study ouabain-induced signalling in neurons, especially the activation of MAPK, because they are the key kinases activated in response to extracellular signals and regulating cell survival, proliferation and apoptosis. In this study we investigated the effect of ouabain on the level of phosphorylation of three MAPK (ERK1/2, JNK and p38) and on cell survival in the primary culture of rat cerebellar cells. Using Western blotting we described the time course and concentration dependence of phosphorylation for ERK1/2, JNK and p38 in response to ouabain. We discovered that ouabain at a concentration of 1 μM does not cause cell death in cultured neurons while it changes the phosphorylation level of the three MAPK: ERK1/2 is phosphorylated transiently, p38 shows sustained phosphorylation, and JNK is dephosphorylated after a long-term incubation. We showed that ERK1/2 phosphorylation increase does not depend on ouabain-induced calcium increase and p38 activation. Changes in p38 phosphorylation, which is independent from ERK1/2 activation, are calcium dependent. Changes in JNK phosphorylation are calcium dependent and also depend on ERK1/2 and p38 activation. Ten-micromolar ouabain leads to cell death, and we conclude that different effects of 1-μM and 10-μM ouabain depend on different ERK1/2 and p38 phosphorylation profiles. Copyright © 2016 John Wiley & Sons, Ltd.

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Endogenous ouabain regulates cell viability

Cited by 64 publications

References 57 publications

Reduction in Maternal Circulating Ouabain Impairs Offspring Growth and Kidney Development

Reduction in Maternal Circulating Ouabain Impairs Offspring Growth and Kidney Development

Estudo dos mecanismos envolvidos no remodelamento de artérias de resistência de ratos hipertensos induzidos pelo tratamento com ouabaína.

Ouabain‐induced changes in MAP kinase phosphorylation in primary culture of rat cerebellar cells

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