Elaidic acid induces cell apoptosis through induction of ROS accumulation and endoplasmic reticulum stress in SH‑SY5Y cells

WW Ma, L Zhao, LH Yuan, HL Yu… - Molecular …, 2017 - spandidos-publications.com
WW Ma, L Zhao, LH Yuan, HL Yu, H Wang, XY Gong, F Wei, R Xiao
Molecular medicine reports, 2017spandidos-publications.com
Elaidic acid, which is a major trans fatty acid, has been reported to be involved in
neurotoxicity; however, the underlying molecular mechanisms underlying its neurotoxic
effects remain largely unknown. Therefore, the present study aimed to investigate the
potential mechanisms underlying elaidic acid‑induced neuronal damage in vitro. The SH‑
SY5Y neuroblastoma cell line was used as a model in the present study. Following
treatment of cells with various concentrations of elaidic acid or with vehicle for 24 h, cell …
Abstract
Elaidic acid, which is a major trans fatty acid, has been reported to be involved in neurotoxicity; however, the underlying molecular mechanisms underlying its neurotoxic effects remain largely unknown. Therefore, the present study aimed to investigate the potential mechanisms underlying elaidic acid‑induced neuronal damage in vitro. The SH‑SY5Y neuroblastoma cell line was used as a model in the present study. Following treatment of cells with various concentrations of elaidic acid or with vehicle for 24 h, cell viability was measured using the MTT assay. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) release were measured using flow cytometry. Cell apoptosis was measured by Annexin V‑fluorescein isothiocyanate/propidium iodide double staining, and cellular redox status was determined using ELISA analysis. Furthermore, western blotting was used to detect the protein expression levels of factors associated with oxidative damage and components of the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) signaling pathways. The results demonstrated that elaidic acid treatment inhibited cell viability, elevated cell apoptosis and resulted in a loss of MMP. In addition, elaidic acid induced marked alterations in cellular redox status. Treatment with high doses of elaidic acid treatment also enhanced the release of ROS, and upregulated lipid peroxide and malondialdehyde levels; however, it reduced superoxide dismutase and glutathione peroxidase activities. Furthermore, elaidic acid resulted in upregulation of nuclear factor erythroid 2‑related factor 2 and downregulation of heme oxygenase 1, which are two key antioxidative factors. Elaidic acid treatment also induced or inhibited the expression of numerous ER stress/UPR‑associated molecules. It induced glucose‑regulated protein 78 (GRP78) expression, whereas the expression levels of activating transcription factor 4 (ATF4) and CCAAT/enhancer‑binding protein homologous protein (CHOP) were upregulated and then downregulated following treatment with various doses of elaidic acid. These results indicated that elaidic acid inhibited SH‑SY5Y cell growth and induced apoptosis by enhancing oxidative stress and activating the ER stress/UPR signaling pathway and the GRP78/ATF4/CHOP pathway.
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