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Fructose‐induced increases in hepatic palmitate perturbs cell Ca2+ and UPR signaling
Author(s) -
Douard Veronique,
Gaspers Lawrence D,
Thomas Andrew P,
Ferraris Ronaldo P
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1116.4
Subject(s) - unfolded protein response , xbp1 , endoplasmic reticulum , apocynin , chemistry , fructose , nadph oxidase , oxidative stress , reactive oxygen species , xanthine oxidase , endocrinology , hepatocyte , medicine , biochemistry , biology , rna splicing , enzyme , rna , in vitro , gene
Fructose (F) is linked to the pathogenesis of fatty liver disease. We recently discovered that F increases levels of reactive oxygen species (ROS) in hepatocytes and that F consumption specifically increases total lipid and palmitate (P) content of the liver. Since P is relatively toxic, here we evaluated whether P by itself induces endoplasmic reticulum (ER) stress thereby altering cell Ca and the unfolded protein response (UPR) known to be associated with oxidative stress and inflammation of the liver. Primary rat hepatocytes exposed to 300 μM P (in BSA) displayed known biomarkers of ER stress by increases in expression of BiP and in splicing of XBP1 (XBP1s). The P‐induced increases in BiP expression and XBP1s are prevented by apocynin and allopurinol, inhibitors of NADPH and xanthine oxidase, respectively, suggesting that P‐induced ROS may contribute to the UPR following F‐induced ER stress. In the presence of glucose, P had little effect on cytosolic Ca ([Ca2+]i) in hepatocytes loaded with fura‐2/AM. In the presence of F, P significantly enhanced fructose‐induced increases in [Ca2+]i, an effect that occurred in >80% of the cells. The addition of BSA alone did not alter [Ca2+]i. Thus, P can act synergistically with F to produce large amplitude [Ca2+]i spikes. Taken together, P does not induce [Ca2+]i spikes independent of F, but may directly affect the UPR (NIH R01AA017752 NSF IBN722365).