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ABC- and SLC-Transporters in Murine and Bovine Mammary Epithelium--Effects of Prochloraz.

Yagdiran Y, Oskarsson A, Knight CH, Tallkvist J - PLoS ONE (2016)

Bottom Line: Gene expressions of BCRP and OCT1 in murine mammary glands were increased during gestation and lactation, whereas MDR1, MRP1, OATP1A5 and OCTN1 were decreased, compared to expressions in virgins.Prochloraz treatment induced MDR1 gene and protein expression in both differentiated HC11 and BME-UV cells and increased protein function in HC11 cells, resulting in decreased accumulation of the MDR1 substrate digoxin.In conclusion, our results demonstrate that murine (HC11) and bovine (BME-UV) mammary epithelial cells can be applied to characterize expression and function of transporters as well as effects of contaminants on the mammary transporters.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden.

ABSTRACT
Some chemicals are ligands to efflux transporters which may result in high concentrations in milk. Limited knowledge is available on the influence of maternal exposure to chemicals on the expression and function of transporters in the lactating mammary gland. We determined gene expression of ABC and SLC transporters in murine mammary tissue of different gestation and lactation stages, in murine mammary cells (HC11) featuring resting and secreting phenotypes and in bovine mammary tissue and cells (BME-UV). Effects on transporter expression and function of the imidazole fungicide prochloraz, previously reported to influence BCRP in mammary cells, was investigated on transporter expression and function in the two cell lines. Transporters studied were BCRP, MDR1, MRP1, OATP1A5/OATP1A2, OCTN1 and OCT1. Gene expressions of BCRP and OCT1 in murine mammary glands were increased during gestation and lactation, whereas MDR1, MRP1, OATP1A5 and OCTN1 were decreased, compared to expressions in virgins. All transporters measured in mammary glands of mice were detected in bovine mammary tissue and in HC11 cells, while only MDR1 and MRP1 were detected in BME-UV cells. Prochloraz treatment induced MDR1 gene and protein expression in both differentiated HC11 and BME-UV cells and increased protein function in HC11 cells, resulting in decreased accumulation of the MDR1 substrate digoxin. In conclusion, our results demonstrate that murine (HC11) and bovine (BME-UV) mammary epithelial cells can be applied to characterize expression and function of transporters as well as effects of contaminants on the mammary transporters. An altered expression, induced by a drug or toxic chemical, on any of the transporters expressed in the mammary epithelial cells during lactation may modulate the well-balanced composition of nutrients and/or secretion of contaminants in milk with potential adverse effects on breast-fed infants and dairy consumers.

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Relative gene expression of MDR1 (A) and MRP1 (B) following prochloraz treatment in BME-UV cells. Normalized gene expressions are presented as means ± SD; n = 8–12 pooled from 2 separate experiments. Statistically significant differences as compared to vehicle controls, **p≤0.01; ***p≤0.001.
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pone.0151904.g006: Relative gene expression of MDR1 (A) and MRP1 (B) following prochloraz treatment in BME-UV cells. Normalized gene expressions are presented as means ± SD; n = 8–12 pooled from 2 separate experiments. Statistically significant differences as compared to vehicle controls, **p≤0.01; ***p≤0.001.

Mentions: In BME-UV cells, gene expressions of MDR1 and MRP1 were induced at the highest concentration of prochloraz (30 μM) (Fig 6A and 6B).


ABC- and SLC-Transporters in Murine and Bovine Mammary Epithelium--Effects of Prochloraz.

Yagdiran Y, Oskarsson A, Knight CH, Tallkvist J - PLoS ONE (2016)

Relative gene expression of MDR1 (A) and MRP1 (B) following prochloraz treatment in BME-UV cells. Normalized gene expressions are presented as means ± SD; n = 8–12 pooled from 2 separate experiments. Statistically significant differences as compared to vehicle controls, **p≤0.01; ***p≤0.001.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4814071&req=5

pone.0151904.g006: Relative gene expression of MDR1 (A) and MRP1 (B) following prochloraz treatment in BME-UV cells. Normalized gene expressions are presented as means ± SD; n = 8–12 pooled from 2 separate experiments. Statistically significant differences as compared to vehicle controls, **p≤0.01; ***p≤0.001.
Mentions: In BME-UV cells, gene expressions of MDR1 and MRP1 were induced at the highest concentration of prochloraz (30 μM) (Fig 6A and 6B).

Bottom Line: Gene expressions of BCRP and OCT1 in murine mammary glands were increased during gestation and lactation, whereas MDR1, MRP1, OATP1A5 and OCTN1 were decreased, compared to expressions in virgins.Prochloraz treatment induced MDR1 gene and protein expression in both differentiated HC11 and BME-UV cells and increased protein function in HC11 cells, resulting in decreased accumulation of the MDR1 substrate digoxin.In conclusion, our results demonstrate that murine (HC11) and bovine (BME-UV) mammary epithelial cells can be applied to characterize expression and function of transporters as well as effects of contaminants on the mammary transporters.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden.

ABSTRACT
Some chemicals are ligands to efflux transporters which may result in high concentrations in milk. Limited knowledge is available on the influence of maternal exposure to chemicals on the expression and function of transporters in the lactating mammary gland. We determined gene expression of ABC and SLC transporters in murine mammary tissue of different gestation and lactation stages, in murine mammary cells (HC11) featuring resting and secreting phenotypes and in bovine mammary tissue and cells (BME-UV). Effects on transporter expression and function of the imidazole fungicide prochloraz, previously reported to influence BCRP in mammary cells, was investigated on transporter expression and function in the two cell lines. Transporters studied were BCRP, MDR1, MRP1, OATP1A5/OATP1A2, OCTN1 and OCT1. Gene expressions of BCRP and OCT1 in murine mammary glands were increased during gestation and lactation, whereas MDR1, MRP1, OATP1A5 and OCTN1 were decreased, compared to expressions in virgins. All transporters measured in mammary glands of mice were detected in bovine mammary tissue and in HC11 cells, while only MDR1 and MRP1 were detected in BME-UV cells. Prochloraz treatment induced MDR1 gene and protein expression in both differentiated HC11 and BME-UV cells and increased protein function in HC11 cells, resulting in decreased accumulation of the MDR1 substrate digoxin. In conclusion, our results demonstrate that murine (HC11) and bovine (BME-UV) mammary epithelial cells can be applied to characterize expression and function of transporters as well as effects of contaminants on the mammary transporters. An altered expression, induced by a drug or toxic chemical, on any of the transporters expressed in the mammary epithelial cells during lactation may modulate the well-balanced composition of nutrients and/or secretion of contaminants in milk with potential adverse effects on breast-fed infants and dairy consumers.

Show MeSH
Related in: MedlinePlus