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  • Bip overexpression, but not CHOP inhibition, attenuates fatty-acid-induced endoplasmic reticulum stress and apoptosis in HepG2 liver cells.

Bip overexpression, but not CHOP inhibition, attenuates fatty-acid-induced endoplasmic reticulum stress and apoptosis in HepG2 liver cells.

Life sciences (2010-10-26)
Xuemei Gu, Kwan Li, D Ross Laybutt, Ming-liang He, Hai-Lu Zhao, Juliana C N Chan, Gang Xu
ABSTRACT

In this study we investigated whether attenuation of endoplasmic reticulum stress (ER stress) could protect HepG2 cells from free fatty acid (FFA)-induced apoptosis. Human liver cell line HepG2 cells were exposed to Sodium Palmitate (Pa) or Sodium Oleate (Ol). Apoptosis and ER stress of HepG2 cells were analyzed with flow cytometry, real-time RT-PCR and Western Blotting. An expression plasmid encoding for the ER chaperone immunoglobulin heavy chain-binding protein (Bip) was transfected into HepG2 cells to attenuate ER stress. Small interfering RNA siCHOP was used to knockdown the expression of C/EBP Homologous Protein (CHOP) in HepG2. Pa led to cytotoxicity and apoptosis in HepG2 cells in a dose-dependent pattern and also induced ER stress indicated by increased phosphorylation of eIF2α, upregulation of IRE1α and CHOP. Bip expression levels were slightly down regulated after Pa treatment. The unsaturated fatty acid, Ol, induced neither apoptosis nor ER stress in HepG2 cells. Overexpression of Bip attenuated Pa-induced ER stress and led to a significant reduction in Pa-mediated apoptosis, indicating a requirement of ER stress for lipotoxicity in liver cells. siRNA-mediated reduction of CHOP did not protect against Pa-induced apoptosis. While ER stress makes a necessary contribution to palmitate cytotoxicity, inhibition of CHOP alone is not sufficient to prevent palmitate-induced apoptosis. Our findings could advance the detailed understanding on the mechanism of high fatty acid (FFA)-induced apoptosis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium oleate, ≥99%
Sigma-Aldrich
Sodium oleate, ≥95% (capillary GC)