Palmitic and linoleic acids induce ER stress and apoptosis in hepatoma cells

Lipids in Health and Disease

Hongyang Shi¹  Xia Yang¹  Zhenni Zhang²  Rongliang Xue²  Yong Zhang² 

[1] Department of Respiration, the Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, West 5th Road, Xi'an, Shaanxi Province-710004, China;Anesthesia Department, the Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, West 5th Road, Xi'an, Shaanxi Province-710004, China

关键词: Thapsigargin;    BAPTA-AM;    Endoplasmic Reticulum Stress;    Linoleic;    Palmitic;    Nonalcoholic fatty liver disease;   

Others  :  1160387
DOI  :  10.1186/1476-511X-11-1

 received in 2011-11-15, accepted in 2012-01-05,  发布年份 2012

【 摘 要 】

Objectives

Hepatic inflammation and degeneration induced by lipid depositions may be the major cause of nonalcoholic fatty liver disease. In this study, we tried to investigate the effects of saturated and unsaturated fatty acids on hepatoma cell apoptosis.

Methods

H4IIE liver cells were treated with palmitic acid, linoleic acid, or both with or without the calcium-specific chelator BAPTA-AM after which the expression of proteins associated with endoplasmic reticulum (ER) stress, apoptosis, caspase-3 levels, and calcium flux were measured.

Results

Palmitic or linoleic acid (250 μM) induced H4IIE cell apoptosis, which required calcium flux but not caspase-3. Apoptosis was not observed when cells were co-treated with linoleic acid (125 μM) and palmitic acid (250 μM). Importantly, the release of cytochrome C from mitochondria into cytoplasm during cell apoptosis was specifically detected only when linoleic acid (125 μM), but not palmitic acid (250 μM), was added to the cells. Depletion of intracellular calcium flux by the calcium-specific chelator, BAPTA-AM, abolished linoleic acid-induced apoptosis. Moreover, in the presence of BAPTA-AM, expression of the unfolded protein response (UPR)-associated genes, CHOP, GRP78, and GRP94, was induced by linoleic acid, but not palmitic acid.

Conclusions

The results suggest that linoleic acid promotes cell apoptosis through the release of cytochrome C, only if the intracellular calcium flux is unperturbed and intact. These results confirm that ER stress contributes to fatty acid-induced liver cell apoptosis.

【 授权许可】

   
2012 Zhang et al; licensee BioMed Central Ltd.

【 图 表 】

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