Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity

Abstract

discovered by Ockner et al. in 1972 ( 2 ) and was originally named Z-protein. Since that time, there has been an explosive growth in information regarding the role of L-FABP in cellular homeostasis. While FABPs are present in many tissues, such as heart, brain, intestinal, skin, adipose, muscle, epidermal, ileal, myelin, and testis, L-FABP is found in abundance in hepatocytes where it accounts for ‫ف‬ 2% of the total cellular protein. Although L-FABP is abundant in the liver, it also is present in tissues such as murine alveolar macrophages ( 3 ), kidney ( 4 ), and intestine ( 5 ).L-FABP is made up of 127 amino acids that compose 10 antiparallel ␤ -strands. These stands are organized into two fi ve-stranded ␤ -sheets and two ␣ -helices. The two ␣ -helices are hypothesized to function as a portal that controls entry and release of ligands from the binding pocket created by the ␤ -strands ( 6 ). A large interior water-fi lled cavity forms the confi nes of the ␤ -strands, which serve as the hydrophobic ligand-binding site. L-FABP is able to bind and translocate many lipophilic substrates throughout the cytosol. Some of these substrates include long-chain fatty acids ( 7-9 ), bile acids ( 10 ), eicosanoids ( 11 ), and hypolipidemic drugs ( 12 ). Transfer of these ligands from L-FABP to membranes is thought to occur by a diffusive process; i.e., the ligand fi rst dissociates from the binding pocket and then diffuses to its site of action, while transfer of ligands from other FABPs, such as I-FABP, is thought to occur by a direct collisional interaction ( 13 ). It seems that L-FABP also plays a role in transferring bound ligands into the nucleus. These ligands could activate the peroxisome proliferator-activated receptor ␣ nuclear receptors and

Susceptibility of L-FABP−/− mice to oxidative stress in early-stage alcoholic liver

“…In addition, L-FABP can bind PUFAs and therefore modulate the availability of these FA to intracellular oxidative pathways ( 52 ). In summary, these data suggest that loss of the primary lipid binding protein in hepatocytes renders FAs freely available for oxidation in systems containing high levels of ROS, including ALD.…”

Amelioration of Angiotensin II–Induced Salt-Sensitive Hypertension by Liver-Type Fatty Acid–Binding Protein in Proximal Tubules

“…The recent study showed that L-FABP has greater hydrophilic antioxidative activity than lipophilic antioxidative activity. 26 These findings indicate that the hydrophilic antioxidative effect of tubular L-FABP in PTCs attenuates AngII-induced SSHT via prevention of AngII-induced ROS generation. Indeed, the present in vitro study demonstrated that AngII-induced intracellular O 2 − generation was significantly attenuated in mProx-L. Interestingly, even rhL-FABP also attenuated the O 2 − generation in mProx as same as mProx-L, suggesting that not only endogenous but also exogenous L-FABP may have hydrophilic antioxidative effect under AngII stimulation.…”

“…25 AngII increases generation of hydrophobic ROS, such as superoxide anion (O 2 − ) and hydrogen peroxide via the action of nicotinamide adenine dinucleotide phosphate oxidase. 23 The antioxidant activity of L-FABP is thought to result from the inactivation of free radicals by methionine and cysteine amino acids in L-FABP and also by exposure of the L-FABP-binding site to lipid peroxides, 26 indicating that L-FABP has both hydrophilic and lipophilic antioxidant effects. The recent study showed that L-FABP has greater hydrophilic antioxidative activity than lipophilic antioxidative activity.…”

Effects of Antioxidants and Additional Emulsifiers on the Stability of Emulsified Milk Fat in the Photo/Radical Oxidation System

“…AAPH is known to be a hydrophilic radical generator and AMVN is known to be a lipophilic radical generator 19 . Here, the radical scavenging activity of Toc at 40 ppm was equivalent to EGCg at 25 ppm, GTE at 23 ppm, Qu at 25 ppm, and RTE at 44 ppm, as described in Section 2.4.…”