In vitro characterization and endocrine regulation of cholesterol and phospholipid transport in the mammary gland

Mol Cell Endocrinol. 2017 Jan 5;439:35-45. doi: 10.1016/j.mce.2016.10.016. Epub 2016 Oct 17.

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.

Keywords: Apolipoprotein A-1; Cholesterol; Efflux; Hormone; Phospholipid; Regulation; Transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / metabolism
  • Animals
  • Apolipoprotein A-I / metabolism
  • Biological Transport / drug effects
  • Biological Transport / genetics
  • Cattle
  • Cell Line
  • Cholesterol / metabolism*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression Regulation / drug effects
  • Homeostasis / drug effects
  • Hormones / pharmacology*
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / metabolism*
  • Membrane Transport Proteins / metabolism
  • Phospholipids / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • ATP Binding Cassette Transporter 1
  • Apolipoprotein A-I
  • Hormones
  • Membrane Transport Proteins
  • Phospholipids
  • RNA, Messenger
  • Cholesterol