High-Density Lipoprotein Prevents Endoplasmic Reticulum Stress-Induced Downregulation of Liver LOX-1 Expression

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Medicine

Background:

• Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediates cellular uptake of oxidized low-density lipoprotein (ox-LDL).
• The effect of high-density lipoprotein (HDL) on endoplasmic reticulum (ER) stress-induced changes in hepatocyte LOX-1 levels is not well understood.

Purpose of the Study:

• To investigate the impact of tunicamycin (TM)-induced ER stress on LOX-1 expression in hepatic L02 cells.
• To determine how HDL influences TM-affected LOX-1 expression and lipid uptake.

Main Methods:

• Tunicamycin (TM) was used to induce ER stress in hepatic L02 cells.
• Gene silencing (IRE1, XBP-1), real-time PCR, western blotting, immunocytochemistry, and DiI-ox-LDL uptake assays were performed.
• Cells were treated with varying concentrations of HDL.

Main Results:

• TM upregulated ER chaperone GRP78 and downregulated LOX-1 expression and lipid uptake.
• Knocking down IRE1 or XBP-1 restored LOX-1 expression and lipid uptake in TM-treated cells.
• HDL treatment prevented TM-induced reductions in LOX-1 expression and lipid uptake, and decreased GRP78, IRE1, and XBP-1 levels.

Conclusions:

• HDL inhibits the IRE1/XBP-1 pathway, preventing ER stress-induced reduction of LOX-1 expression in hepatocytes.
• This mechanism highlights a novel role for HDL in improving lipid metabolism.