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

Abstract

ObjectivesHepatic 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.MethodsH4IIE 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.ResultsPalmitic 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.ConclusionsThe 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.

Biochemical and physical kernel properties of a standard maize hybrid in different TopCross™ Blends

“…Maize kernel contains an average fatty acid composition of 11 % palmitic (16:0), 2 % stearic (18:0), 24 % oleic (18:1), 62 % linoleic (18:2) and 1 % linolenic (18:3) acids (Weber, 1987). Unsaturated fatty acids are considered healthier because they have a positive influence on reducing serum cholesterol and low density lipoproteins (Mattson and Grundy, 1985), as well as on preventing degenerative diseases and cancer (Mattson and Grundy, 1985;Zhang et al, 2012). On the other hand, increased saturated (palmitic and stearic) fatty acids can enable production of margarines without hydrogenation and the subsequent formation of undesirable trans fatty acids (Duvick et al, 2006).…”

Palmitic Acid Increases Endothelin-1 Expression in Vascular Endothelial Cells through the Induction of Endoplasmic Reticulum Stress and Protein Kinase C Signaling

“…It has previously been shown that PA induces ER stress in many different cell species [39][40][41]. We wondered whether PA treatment causes ER stress to cultured HAECs by determining the expression of CHOP, a marker of ER stress response [42].…”

ω-Hydroxyundec-9-enoic acid induces apoptosis through ROS-mediated endoplasmic reticulum stress in non-small cell lung cancer cells

“…Some fatty acids attenuate growth and induce apoptosis in a variety of human cancer cell lines [3][4][5]8,9,13,14,[16][17][18]. Fatty acid-induced apoptosis may be correlated with increased activity of caspases [4,7,16,17].…”

“…Some fatty acids such as polyunsaturated linoleic acid and saturated palmitic acid are known to induce ER stress [13]. To investigate whether x-HUA treatment causes ER stress, ER-specific signals were measured.…”