The unfolded protein response is a negative regulator of scavenger receptor class B, type I (SR-BI) expression

Tanja Eberhart, Karin Eigner, Yüksel Filik, Stefanie Fruhwürth, Herbert Stangl, Clemens Röhrl

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Scavenger receptor class B, type I (SR-BI) is the main receptor for high-density lipoprotein (HDL) and an emerging atheroprotective candidate. A central function of SR-BI is the delivery of HDL-derived cholesterol to the liver for subsequent excretion into the bile. Here, we investigated the regulation of SR-BI by the unfolded protein response (UPR), an adaptive mechanism induced by endoplasmic reticulum (ER) stress, which is frequently activated in metabolic disorders. We provide evidence that induction of acute ER stress by well-characterized chemical inducers leads to decreased SR-BI expression in hepatocyte-derived cell lines. This results in a functional reduction of selective lipid uptake from HDL. However, the regulation of SR-BI by ER stress is not a direct consequence of altered cellular cholesterol metabolism. Finally, we show that SR-BI down-regulation by the UPR might be a compensatory mechanism to provide partial adaption to ER stress. The observed down-regulation of SR-BI by ER stress in hepatic cells might contribute to the unfavorable effects of metabolic disorders on cholesterol homeostasis and cardiovascular diseases.

Original languageEnglish
Pages (from-to)557-562
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume479
Issue number3
DOIs
Publication statusPublished - 21 Oct 2016
Externally publishedYes

Keywords

  • Cholesterol
  • Endoplasmic reticulum stress (ER stress)
  • HDL
  • Unfolded protein response (UPR)
  • Cell Line
  • Cholesterol/chemistry
  • Cardiovascular Diseases/metabolism
  • Down-Regulation
  • Humans
  • Gene Expression Regulation
  • Homeostasis
  • Scavenger Receptors, Class B/metabolism
  • Lipids/chemistry
  • Unfolded Protein Response
  • Hep G2 Cells
  • RNA, Small Interfering/metabolism
  • Endoplasmic Reticulum Stress
  • Cell Line, Tumor
  • Hepatocytes/cytology
  • Endoplasmic Reticulum/metabolism

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