Antioxidative Function of L-FABP in L-FABP Stably Transfected Chang Liver Cells *

Abstract

C ellular oxidative stress is one of the factors responsible for the propagation of liver diseases, such as hepatitis, cirrhosis, and hepatoma. 1 Several primary antioxidant defense systems such as superoxide dismutase (SOD), catalase, glutathione (GSH), and glutathione peroxidase are present intracellularly. These systems scavenge reactive oxygen species (ROS) such as hydrogen peroxide, superoxide, lipid peroxides, and free radicals. Exposure to oxidative stress may, however, deplete the cellular antioxidant capacity. Therefore, other antioxidant defense systems are expected to play an important role in oxidative stress.Liver fatty acid binding protein (L-FABP) is a 14-kd protein found abundantly in the cytoplasm and the nucleus of hepatocytes. 2,3 L-FABP is very likely to be an effective endogenous antioxidant, because it has high affinity and capacity to bind long-chain fatty acid oxidation products. 4,5 Hepatocyte L-FABP concentration could be as high as 0.4 mmol/L, 6 and it contains a large number of reducing amino acid residues (1 cysteine and 7 methionine residues) in its molecular structure. With an accessible volume enclosed by the molecular surface of L-FABP of 28,600 Å 3,7 the concentration of total methionine residues in L-FABP could be as high as approximately 400 mmol/L. Methionine and cysteine amino acids are regarded as cellular scavengers of activated xenobiotics and

Intestinal Glucose Uptake Protects Liver from Lipopolysaccharide and d-Galactosamine, Acetaminophen, and Alpha-Amanitin in Mice

“…In the liver of LPS/D-GalNtreated mice, numerous apoptotic cells were detected by TUNEL assay ( Figure 2E), while in animals treated with D-glucose, the staining for apoptotic nuclei is negative ( Figure 2F). Analysis of two markers of liver injury, ie, ALT and LDH 11,12 in the sera of the different groups of mice, measured 6 hours after LPS/D-GalN administration, further confirmed the protective effect of D-glucose; in fact, the strong increase of plasma ALT and LDH levels observed after LPS/D-GalN administration was significantly reduced in D-glucose pretreated mice (ALT: During LPS/D-GalN intoxication, ICAM-1 expression in hepatocytes and nonparenchymal cells is enhanced. Upregulation of this molecule is necessary for extravasation, into the liver parenchyma, of neutrophils, which produce cytotoxic damage to hepatocytes.…”

Identification of biomarkers associated with the development of hepatocellular carcinoma in CuZn superoxide dismutase deficient mice

“…Deletion of FABP1 in mutant mice causes problem in branched-chain fatty acid metabolism [41]. A recent study showed the antioxidant function of FABP1, and increased expression of FABP1 in a liver cell line reduced cellular damage from hypoxia/reoxygenation [42]. Therefore, similar to CAIII deficiency, reduced FABP1 may contribute to a further increase in oxidative damage in Sod1−/− mice.…”

The antifibrogenic effect of (−)-epigallocatechin gallate results from the induction of de novo synthesis of glutathione in passaged rat hepatic stellate cells

“…24 Briefly, 2,7-dichlorofluorescein diacetate (DCFH-DA, Molecular Probes Inc., Eugene, OR, USA) was applied to the culture medium after exposure to EGCG at various concentrations or other reagents. Fluorescent units were measured in each well after 45-min incubation with DCF (5 mM) with excitation wavelength of 485 nm and emission wavelength of 530 nm using a fluorescence multiwell plate reader (Genios Plus, Tecan, San Jose, CA, USA).…”