Role of cytosolic liver fatty acid binding protein in hepatocellular oxidative stress: effect of dexamethasone and clofibrate treatment.
The presence of cysteine and methionine groups together with an ability to bind long-chain fatty acid (LCFA) oxidation products makes liver fatty acid binding protein (L-FABP) an attractive candidate against hepatocellular oxidative stress. In this report, we show that pharmacological treatment directed at modulating L-FABP level affected hepatocellular oxidant status. L-FABP expressing 1548-hepatoma cells, treated with dexamethasone or clofibrate, decreased and increased intracellular L-FABP levels, respectively. Oxidative stress was induced by H2O2 incubation or hypoxia-reoxygenation. The fluorescent marker, dichlorofluorescein (DCF), was employed to measure intracellular reactive oxygen species (ROS). Hepatocellular damage was assessed by lactate dehydrogenase (LDH) level. Dexamethasone treatment resulted in a significant increase in DCF fluorescence with higher LDH release compared to control cells. Clofibrate treatment, however, resulted in a significant decrease in both parameters (p<0.05). Drug treatments did not affect cytosolic activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), or catalase suggesting that the differences between treated and control cells may likely be associated with varying L-FABP levels. We conclude that L-FABP may act as an effective endogenous cytoprotectant against hepatocellular oxidative stress.
Rajaraman
G
G
Faculty of Pharmacy, University of Manitoba, 50 Sifton Road, R3T 2N2, Winnipeg, Manitoba, Canada.
Wang
G Q
GQ
Yan
J
J
Jiang
P
P
Gong
Y
Y
Burczynski
F J
FJ
D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D002374:Catalase / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002994:Clofibrate / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005452:Fluoresceins / Q000378:metabolism; D005453:Fluorescence; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism
D050556:Fatty Acid-Binding Proteins; D005452:Fluoresceins; C037631:2',7'-dichlorofluorescein; D003907:Dexamethasone; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D002994:Clofibrate