title: In vitro characterization and endocrine regulation of cholesterol and phospholipid transport in the mammary gland.
abstract: Cell-based studies previously showed that the ATP-binding cassette transporter A1 (ABCA1) transfers cholesterol across mammary epithelial cells (MEC). Data for phospholipid transport are lacking, and it is unclear from which cellular source the transported cholesterol stems, whether this transport activates signaling pathways, and how lactogenic hormones regulate it. To clarify these aspects, lipid transport and expressional analyses were performed in bovine primary (bMEC) and/or immortalized (MAC-T) MEC cultures. Lipid efflux and ABCA1, ABCG1 and liver X receptorα mRNA levels were higher in MAC-T than bMEC. In MAC-T, the transported cholesterol originated mainly from the plasma membrane. ABCA1 dependent cholesterol efflux was higher than phosphatidylcholine efflux, was suppressed by probucol (ABCA1 inhibitor), AG490 (janus kinase-2 inhibitor), PD98059 (mitogen activated protein kinase kinase inhibitor) and pretreatment with β-cyclodextrin (lowering membrane cholesterol). Insulin was the only hormone significantly increasing cholesterol efflux. In conclusion, this study gives novel mechanistic and regulatory insights into the transport of cholesterol and phospholipids in MEC.
authors.affiliation: Institute of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Bern, Buehlstrasse 28, 3012, Bern, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland.
authors.forename: Corneille Edgar
authors.initials: CE
authors.lastname: Ontsouka
authors.affiliation: Institute of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Bern, Buehlstrasse 28, 3012, Bern, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland.
authors.forename: Xiao
authors.initials: X
authors.lastname: Huang
authors.affiliation: Institute of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Bern, Buehlstrasse 28, 3012, Bern, Switzerland.
authors.forename: Eldar
authors.initials: E
authors.lastname: Aliyev
authors.affiliation: Institute of Biochemistry and Molecular Medicine, Faculty of Medicine, University of Bern, Buehlstrasse 28, 3012, Bern, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland. Electronic address: christiane.albrecht@ibmm.unibe.ch.
authors.forename: Christiane
authors.initials: C
authors.lastname: Albrecht
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D002417:Cattle; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D006728:Hormones; D026901:Membrane Transport Proteins; D010743:Phospholipids; D012333:RNA, Messenger; D002784:Cholesterol
keywords: Apolipoprotein A-1; Cholesterol; Efflux; Hormone; Phospholipid; Regulation; Transport