Expression, localization, and functional model of cholesterol transporters in lactating and nonlactating mammary tissues of murine, bovine, and human origin.
Members of the ATP-binding cassette (ABC) transporters play a pivotal role in cellular lipid efflux. To identify candidate cholesterol transporters implicated in lipid homeostasis and mammary gland (MG) physiology, we compared expression and localization of ABCA1, ABCG1, and ABCA7 and their regulatory genes in mammary tissues of different species during the pregnancy-lactation cycle. Murine and bovine mammary glands (MGs) were investigated during different functional stages. The abundance of mRNAs was determined by quantitative RT-PCR. Furthermore, transporter proteins were localized in murine, bovine, and human MGs by immunohistochemistry. In the murine MG, ABCA1 mRNA abundance was elevated during nonlactating compared with lactating stages, whereas ABCA7 and ABCA1 mRNA profiles were not altered. In the bovine MG, ABCA1, ABCG1, and ABCA7 mRNAs abundances were increased during nonlactating stages compared with lactation. Furthermore, associations between mRNA levels of transporters and their regulatory genes LXRalpha, PPARgamma, and SREBPs were found. ABCA1, ABCG1, and ABCA7 proteins were localized in glandular MG epithelial cells (MEC) during lactation, whereas during nonlactating stages, depending on species, the proteins showed distinct localization patterns in MEC and adipocytes. Our results demonstrate that ABCA1, ABCG1, and ABCA7 are differentially expressed between lactation and nonlactating stages and in association with regulatory genes. Combined expression and localization data suggest that the selected cholesterol transporters are universal MG transporters involved in transport and storage of cholesterol and in lipid homeostasis of MEC. Because of the species-specific expression patterns of transporters in mammary tissue, mechanisms of cholesterol homeostasis seem to be differentially regulated between species.
Mani
Orlando
O
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
Körner
Meike
M
Sorensen
Martin T
MT
Sejrsen
Kristen
K
Wotzkow
Carlos
C
Ontsouka
Corneille E
CE
Friis
Robert R
RR
Bruckmaier
Rupert M
RM
Albrecht
Christiane
C
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007774:Lactation / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism; D000071518:Liver X Receptors; D008321:Mammary Glands, Animal / Q000378:metabolism*; D042361:Mammary Glands, Human / Q000378:metabolism*; D051379:Mice; D057093:Orphan Nuclear Receptors / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics
C577836:ABCA1 protein, human; C411895:ABCA7 protein, human; C419353:ABCG1 protein, human; C487540:ABCG1 protein, mouse; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; C485856:Abca7 protein, mouse; D008074:Lipoproteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D012333:RNA, Messenger; D051779:Sterol Regulatory Element Binding Proteins; D002784:Cholesterol