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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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Related in: MedlinePlus

Cell viability in HC11 and BME-UV cells treated with prochloraz for 24h.The data represent means ± SD; n = 6. Statistically significant differences as compared to vehicle controls *p≤0.01. Experiment repeated twice and data shown from one representative experiment.
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pone.0151904.g004: Cell viability in HC11 and BME-UV cells treated with prochloraz for 24h.The data represent means ± SD; n = 6. Statistically significant differences as compared to vehicle controls *p≤0.01. Experiment repeated twice and data shown from one representative experiment.

Mentions: Cell viability after prochloraz treatment of cells was assessed by MTS. For both cell lines cell viability remained >80% after incubation with prochloraz up to 30 μM compared to vehicle control and declined dramatically after treatment with 100 μM prochloraz (Fig 4).


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

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

Cell viability in HC11 and BME-UV cells treated with prochloraz for 24h.The data represent means ± SD; n = 6. Statistically significant differences as compared to vehicle controls *p≤0.01. Experiment repeated twice and data shown from one representative experiment.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0151904.g004: Cell viability in HC11 and BME-UV cells treated with prochloraz for 24h.The data represent means ± SD; n = 6. Statistically significant differences as compared to vehicle controls *p≤0.01. Experiment repeated twice and data shown from one representative experiment.
Mentions: Cell viability after prochloraz treatment of cells was assessed by MTS. For both cell lines cell viability remained >80% after incubation with prochloraz up to 30 μM compared to vehicle control and declined dramatically after treatment with 100 μM prochloraz (Fig 4).

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