{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:03:46Z","timestamp":1762542226287},"reference-count":65,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2014,3,1]]},"abstract":"<jats:p> Cellular mechanisms to account for the low Na<jats:sup>+<\/jats:sup> concentration in human milk are poorly defined. MCF10A cells, which were derived from human mammary epithelium and grown on permeable supports, exhibit amiloride- and benzamil-sensitive short-circuit current ( I<jats:sub>sc<\/jats:sub>; a sensitive indicator of net ion transport), suggesting activity of the epithelial Na<jats:sup>+<\/jats:sup> channel ENaC. When cultured in the presence of cholera toxin (Ctx), MCF10A cells exhibit greater amiloride-sensitive I<jats:sub>sc<\/jats:sub> at all time points tested (2 h to 7 days), an effect that is not reduced with Ctx washout for 12 h. Amiloride-sensitive I<jats:sub>sc<\/jats:sub> remains elevated by Ctx in the presence of inhibitors for PKA (H-89, R<jats:sub>p<\/jats:sub>-cAMP), PI3K (LY294002), and protein trafficking (brefeldin A). Additionally, the Ctx B subunit, alone, does not replicate these effects. RT-PCR and Western blot analyses indicate no significant increase in either the mRNA or protein expression for \u03b1-, \u03b2-, or, \u03b3-ENaC subunits. Ctx increases the abundance of both \u03b2- and \u03b3-ENaC in the apical membrane. Additionally, Ctx increases both phosphorylated and nonphosphorylated Nedd4-2 expression. These results demonstrate that human mammary epithelia express ENaC, which can account for the low Na<jats:sup>+<\/jats:sup> concentration in milk. Importantly, the results suggest that Ctx increases the expression but reduces the activity of the E3 ubiquitin ligase Nedd4-2, which would tend to reduce the ENaC retrieval and increase steady-state membrane residency. The results reveal a novel mechanism in human mammary gland epithelia by which Ctx regulates ENaC-mediated Na<jats:sup>+<\/jats:sup> transport, which may have inferences for epithelial ion transport regulation in other tissues throughout the body. <\/jats:p>","DOI":"10.1152\/ajpcell.00181.2013","type":"journal-article","created":{"date-parts":[[2013,12,27]],"date-time":"2013-12-27T02:34:11Z","timestamp":1388111651000},"page":"C471-C484","source":"Crossref","is-referenced-by-count":4,"title":["Cholera toxin enhances Na<sup>+<\/sup> absorption across MCF10A human mammary epithelia"],"prefix":"10.1152","volume":"306","author":[{"given":"Qian","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce D.","family":"Schultz","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, Kansas State University, 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