TY - JOUR
T1 - The unfolded protein response is a negative regulator of scavenger receptor class B, type I (SR-BI) expression
AU - Eberhart, Tanja
AU - Eigner, Karin
AU - Filik, Yüksel
AU - Fruhwürth, Stefanie
AU - Stangl, Herbert
AU - Röhrl, Clemens
N1 - Funding Information:
This study was supported by a grant of the Herzfelder'sche Familienstiftung (to Clemens Röhrl). We are grateful to Ingrid Hassl for excellent technical assistance.
Publisher Copyright:
© 2016 The Author(s)
PY - 2016/10/21
Y1 - 2016/10/21
N2 - 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.
AB - 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.
KW - Cholesterol
KW - Endoplasmic reticulum stress (ER stress)
KW - HDL
KW - Unfolded protein response (UPR)
KW - Cell Line
KW - Cholesterol/chemistry
KW - Cardiovascular Diseases/metabolism
KW - Down-Regulation
KW - Humans
KW - Gene Expression Regulation
KW - Homeostasis
KW - Scavenger Receptors, Class B/metabolism
KW - Lipids/chemistry
KW - Unfolded Protein Response
KW - Hep G2 Cells
KW - RNA, Small Interfering/metabolism
KW - Endoplasmic Reticulum Stress
KW - Cell Line, Tumor
KW - Hepatocytes/cytology
KW - Endoplasmic Reticulum/metabolism
UR - http://www.scopus.com/inward/record.url?scp=84989876164&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2016.09.110
DO - 10.1016/j.bbrc.2016.09.110
M3 - Article
C2 - 27666478
AN - SCOPUS:84989876164
SN - 0006-291X
VL - 479
SP - 557
EP - 562
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
