New Insights into the Regulation of Na+,K+-ATPase by Ouabain

Silva, Elisabete; Soares-da-Silva, Patrı́cio

doi:10.1016/b978-0-12-394305-7.00002-1

Cited by 49 publications

(33 citation statements)

References 189 publications

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“…NKA is a primary active transporter of 3 Na ϩ outward and 2 K ϩ inward located in the basolateral membrane (BLM) of all epithelial cells (127). It integrates an ␣-subunit, responsible for ion movement and various binding sites, and a ␤-subunit, required for the correct enzyme assembly and membrane targeting.…”

Section: Healthy Intestinal Tract Epitheliummentioning

confidence: 99%

Role of epithelial ion transports in inflammatory bowel disease

Magalhães

Cabral

Soares‐da‐Silva

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with a complex pathogenesis. Diarrhea is a highly prevalent and often debilitating symptom of IBD patients that results, at least in part, from an intestinal hydroelectrolytic imbalance. Evidence suggests that reduced electrolyte absorption is more relevant than increased secretion to this disequilibrium. This systematic review analyses and integrates the current evidence on the roles of epithelial Na+-K+-ATPase (NKA), Na+/H+ exchangers (NHEs), epithelial Na+ channels (ENaC), and K+ channels (KC) in IBD-associated diarrhea. NKA is the key driving force of the transepithelial ionic transport and its activity is decreased in IBD. In addition, the downregulation of apical NHE and ENaC and the upregulation of apical large-conductance KC all contribute to the IBD-associated diarrhea by lowering sodium absorption and/or increasing potassium secretion.

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Section: Healthy Intestinal Tract Epitheliummentioning

confidence: 99%

Role of epithelial ion transports in inflammatory bowel disease

Magalhães

Cabral

Soares‐da‐Silva

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Among the various cascades activated are Src, 1,4,5-triphosphate receptor that regulates the mitogen-activated protein kinase pathway, reactive oxygen species, and intracellular Ca 2+ oscillations. [7][8][9] Some of these pathways are tightly involved in the regulation of cell growth. 10 Indeed, ouabain has been shown to induce stimulatory and inhibitory effects on cell viability and proliferation: The addition of relatively low concentrations of ouabain induces proliferation of several cell types, whereas higher concentrations lead to apoptosis.…”

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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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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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“…Although most CGs are derived from plants, several CGs have been identified in mammalian tissues including ouabain, marinobufagenin, and digoxin (3,4). It is clear today that CGs are synthesized in the adrenal glands and function as endogenous hormones, but their exact roles and cellular functions are poorly understood (5).…”

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confidence: 99%