α-Linolenic acid prevents endoplasmic reticulum stress-mediated apoptosis of stearic acid lipotoxicity on primary rat hepatocytes

Lipids in Health and Disease

Research

Li Zhang¹  Lei Dong¹  Yong Zhang¹  Hongyang Shi²  Xia Yang² 

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

关键词: Stearic Acid;    Endoplasmic Reticulum Stress;    Unfold Protein Response;    Thapsigargin;    Nonalcoholic Fatty Liver Disease;   

DOI  :  10.1186/1476-511X-10-81

 received in 2010-09-07, accepted in 2011-05-18,  发布年份 2011

来源: Springer

【 摘 要 】

AimsLipid accumulation in non-adipose tissues leads to cell dysfunction and apoptosis, a phenomenon known as lipotoxicity. Unsaturated fatty acids may offset the lipotoxicity associated with saturated fatty acids. Stearic acid induced endoplasmic reticulum (ER) stress and caused apoptotic and necrotic cell death in the primary rat hepatocytes.MethodsCell viability was investigated using MTT assay, and apoptosis was evaluated with Hoechst 33342 staining. Western blot analysis was used to examine the changes in the expression levels of glucose regulated protein 78 (GRP78), glucose regulated protein 94 (GRP94), and C/EBP homologous protein (CHOP). Caspase-3 activity was evaluated using a Caspase-3 substrate kit.ResultsWe have studied the ability of α-linolenic acid to prevent endoplasmic reticulum stress-mediated apoptosis of rat hepatocytes elicited by stearic acid and thapsigargin. Incubation of primary rat hepatocytes for 16 h with stearic acid produced a significant increase in cell death. Stearic acid also increased levels of three indicators of ER stress -- GRP78, CHOP, and GRP94. α-Linolenic acid distinctly reduced cell death and levels of all three indicators of ER stress brought about by stearic acid. Thapsigargin, which induces ER stress produced similar effects to those obtained using stearic acid; its effects were partly reversed by α-linolenic acid.ConclusionThese results suggest that α-linolenic acid prevents ER stress-mediated apoptosis of stearic acid lipotoxicity on primary rat hepatocytes might become a target to develop new antiapoptotic compounds in nonalcoholic fatty liver disease (NAFLD).

【 授权许可】

Unknown   
© Zhang et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.