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Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland.

ABSTRACT: Transporters involved in bile acid (BA) handling by the mammary gland are poorly understood. Here we have investigated the role of ABC proteins in blood-milk BA traffic and its sensitivity to maternal cholestasis. BA concentrations in rat and mouse serum were higher than in milk. BA profiles in both fluids were also different. In mammary gland, mRNA levels of ABC pumps transporting BAs were high for Bcrp, less abundant for Mrp1, Mrp3 and Mrp4 and negligible for Bsep and Mrp2. Milk BA concentrations were lower in Abcg2 ^-/- than in wild-type mice. Taurocholate administration (5?µmol, i.p.) increased 20-fold BA concentrations in serum, but only moderately in milk, even in Abcg2 ^-/- mice. Bile duct ligation (BDL) in pregnant rats markedly increased serum BA concentrations, which was not proportionally reflected in milk. In rat mammary tissue, Mrp4 was up-regulated by BDL. Serum BA levels were 2-fold higher in 10-day-old neonates of the BDL group, whereas their body weight was lower. The exchange of breastfeeding mothers immediately after birth reverted the situation without changes in endogenous BA synthesis. In conclusion, Bcrp is involved in BA secretion into milk, whereas Mrp4 participates in a blood-milk barrier that protects neonates from maternal hypercholanemia during breastfeeding.

SUBMITTER: Blazquez AMG

PROVIDER: S-EPMC5547141 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland.

Blazquez Alba M G AMG Macias Rocio I R RIR Cives-Losada Candela C de la Iglesia Alberto A Marin Jose J G JJG Monte Maria J MJ

Scientific reports 20170807 1

Transporters involved in bile acid (BA) handling by the mammary gland are poorly understood. Here we have investigated the role of ABC proteins in blood-milk BA traffic and its sensitivity to maternal cholestasis. BA concentrations in rat and mouse serum were higher than in milk. BA profiles in both fluids were also different. In mammary gland, mRNA levels of ABC pumps transporting BAs were high for Bcrp, less abundant for Mrp1, Mrp3 and Mrp4 and negligible for Bsep and Mrp2. Milk BA concentrati ...[more]

PMID: 28785115

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Project description:BackgroundMilk protein is crucial for milk quality in sows and health of newborn piglets. Plasma amino acids (AA) in sows are important precursors for milk protein synthesis in the mammary gland. In order to study the regulation of AA transported in sow mammary glands and possible underlying mechanisms, we measured the expression of genes coding for milk proteins, AA transporter expressions, and plasma AA concentrations in sows at three different physiological stages (D-17, D1 and D17 of lactation), and then further investigated the regulation of AA transport across the cell membrane by adaptive mechanisms using pig mammary epithelial cells (PMEC) as an in vitro model. PMEC were cultured in DMEM:F12 with 4 amino acid concentrations (0 × AA complex, 1 × AA complex, 5 × AA complex, and 25 × AA complex). Classes of AA complexes evaluated in this study included neutral AAs (L-Ala + L-Ser + L-Cys), acidic AAs (L-Asp, L-Glu) and neutral + basic AAs (L-Ala + L-Ser + L-Cys + L-Lys).ResultsOur results indicated that mRNA expression of genes coding for milk protein (αs1-casein, αs2-casein, β-casein and κ-casein) increased significantly with the advance of physiological stage (P < 0.05), and plasma concentrations of most AAs including threonine, serine, glutamate, alanine, valine, cysteine, methionine, isoleucine and tyrosine were greater at D1 of lactation compared with D-17 and D17 of lactation (P < 0.05). Additionally, protein and gene expressions of AA transporters including excitatory AA transporter 3 (EAAT3), alanine/serine/cysteine/threonine transporter (ASCT1) and sodium-coupled neutral AA transporter 1 (SNAT2) were greater in lactating sow mammary glands compared with sow mammary glands in late pregnancy (P < 0.05). The mRNA expressions of SLC38A2, SLC1A1, SLC6A14 increased significantly in the cell mediums supplemented with 5 × and 25 × of AA complexes compared with those cells cultured in DMEM/F12 cell medium (P < 0.05). The mRNA expressions of SLC38A, SLC1A4, and SLC6A14 also increased in EBSS cell medium compared to DMEM/F12. However, only mRNA expression of SLC38A decreased when AA complex was added into EBSS (P < 0.05).ConclusionAA transportation was positively regulated in sow mammary glands with the advance of physiological stage from late pregnancy to peak of lactation and AA transporters in PMECs were adaptively regulated by changed AA concentrations.

Dataset Information

Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland.

Publications

Lactation during cholestasis: Role of ABC proteins in bile acid traffic across the mammary gland.

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