Amino acid exchange and covalent modification by cysteine and glutathione explain isoforms of fatty acid-binding protein occurring in bovine liver

Dormann, P.; Börchers, Torsten; Korf, U.; Højrup, Peter; Roepstorff, Peter; Spener, Friedrich

doi:10.1016/s0021-9258(19)85418-2

Cited by 42 publications

(7 citation statements)

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“…1A ). As expected, the deduced amino acid sequence showed high identity to that of other known L-FABP sequences i.e., 94, 84, 81, and 75% to L-FABPs from rat (9), human (8), pig (10), and cattle (29), respectively. The full-length murine L-FABP cDNA was used as template to amplify the coding region by PCR with oligonucleotide primers 5 Ј -GCCCATATGA ACTTCTCCGG-3 Ј and 5 Ј -NNGGATCCTAAATTCTCTTGCTG-3 Ј using Pfu polymerase.…”

Section: Cloning Of Murine L-fabp Cdnasupporting

confidence: 73%

Phytanic acid is ligand and transcriptional activator of murine liver fatty acid binding protein

Wolfrum

Ellinghaus²,

Fobker³

et al. 1999

Journal of Lipid Research

116

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Branched-chain phytanic acid is metabolized in liver peroxisomes. Sterol carrier protein 2/sterol carrier protein x (SCP2/SCPx) knockout mice, which develop a phenotype with a deficiency in phytanic acid degradation, accumulate dramatically high concentrations of this fatty acid in serum (Seedorf at al. 1998. Genes Dev. 12: 1189-1201) and liver. Concomitantly, a 6.9-fold induction of liver fatty acid binding protein (L-FABP) expression is observed in comparison to wild-type animals fed standard chow, possibly mediated by the peroxisome proliferator-activated receptor alpha (PPAR ␣ ). Cytosolic transport of phytanic acid to either peroxisomal membranes or to the nucleus for activation of PPAR ␣ may be mediated by L-FABP, which gives rise to the question whether phytanic acid is a transactivator of this protein. Here we show first that phytanic acid binds to recombinant L-FABP with high affinity. Then the increase of the in vivo phytanic acid concentration by phytol feeding to mice results in a 4-fold induction of L-FABP expression in liver, which is in the order of that attained with bezafibrate, a known peroxisome proliferator. Finally to test in vitro whether this induction is conferred by phytanic acid, we cotransfected HepG2 cells with an expression plasmid for murine PPAR ␣ and a CAT-reporter gene with 176 bp of the murine L-FABP promoter, containing the peroxisome proliferator responsive element (PPRE). After incubation with phytanic acid, we observed a 3.2-fold induction of CAT expression.These findings, both in vivo and in vitro, demonstrate that phytanic acid is a transscriptional activator of L-FABP expression and that this effect is mediated via PPAR ␣ . -Wolfrum, C., P. Ellinghaus, M. Fobker, U. Seedorf, G. Assmann, T. Börchers, and F. Spener. Phytanic acid is ligand and transcriptional activator of murine liver fatty acid binding protein.

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Section: Cloning Of Murine L-fabp Cdnasupporting

confidence: 73%

Phytanic acid is ligand and transcriptional activator of murine liver fatty acid binding protein

Wolfrum

Ellinghaus²,

Fobker³

et al. 1999

Journal of Lipid Research

116

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“…An intriguing feature of most FABPs, except adipocyte FABP (Matarese et al, 1989), is additional heterogeneity demonstrated by the presence of isoforms such as those observed with fatty acid binding proteins from liver (Dormann et al, 1993;Das et al, 1989;Haunerland et al, 1984;Ketterer et al, 1976;Matarese et al, 1989), heart (Bartetzko et al 1993;Unterberg et al, 1990), adipocyte (Matarese et al, 1989), myelin [reviewed in Matarese et al (1989)], fetal lung (Sa et al, 1993), and placenta (Das et al, 1988). However, the molecular basis of this heterogeneity (bound ligand, multiple mRNAs, deamidation, decarboxylation, tyrosine phosphorylation or cysteine modification, etc.)…”

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confidence: 99%

“…does not appear to be resolved conclusively in the literature [reviewed in Matarese et al (1989)]. There is evidence suggesting that L-FABP isoforms were not due to deamidation, multiple mRNAs, decarboxylation, or tyrosine phosphorylation but instead may result from the presence of noncovalently bound ligands (fatty acid) (Spener et al, 1990;Bass, 1985;Trulzsch & Arias, 1981), interactions with isoelectric focusing ampholytes (Ketterer et al, 1976), or cysteine modification (Sato et al, 1996;Dormann et al, 1993;Hitomi et al, 1990).…”

mentioning

confidence: 99%

“…The secondary and tertiary structures of apo-and holo-FABPs (e.g., those from intestine, heart, and adipocyte) have been extensively investigated by NMR, X-ray crystallography, fluorescence, and circular dichroism [reviewed in Sacchettini and Gordon (1993) and Matarese et al (1989)]. In contrast, while the primary structure of apo-FABP isoforms has been obtained by protein amino acid sequencing (Sato et al, 1996;Hitomi et al, 1990;Dormann et al, 1993;Haunerland et al, 1984) or cDNA characterization (Bartetzko et al, 1993), very little is known about the secondary and the tertiary structure of either FABPs resolved into isoforms (Li & Ishibashi, 1992;Schulenberg-Schell et al, 1988).…”

mentioning

confidence: 99%

“…Fatty acyl CoAs are extremely important in view of their involvement not only in the intermediary metabolism of fatty acids, but also in the regulation (at nM levels) of many intracellular functions including signal transduction and gene transcription [reviewed in Raman and DiRusso (1995), Dedukhova et al (1991), Nikawa et al (1979), Oram et al (1975), and Gossett et al (1996]. Finally, there is evidence suggesting that FABP isoforms may have physiological roles related to the redox status of the cell (Sato et al, 1996;Dormann et al, 1993), intracellular targeting (Unterberg et al, 1990), ligand binding (Sha et al, 1993), and regulation of enzyme activity (Miyozawa & Hashimoto, 1979;Buhr et al, 1994;Sa et al, 1989;Das et al, 1989).…”

mentioning

confidence: 99%

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Isoforms of Rat Liver Fatty Acid Binding Protein Differ in Structure and Affinity for Fatty Acids and Fatty Acyl CoAs

et al. 1997

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Although native rat liver fatty acid binding protein (L-FABP) is composed of isoforms differing in isoelectric point, their comparative structure and function are unknown. These properties of apo- and holo-L-FABP isoforms were resolved by circular dichroism, time-resolved fluorescence spectroscopy, and binding/displacement of fluorescent ligands. Both apo-isoforms had similar hydrodynamic radii of 18.5 A, but apo-isoform I had a greater alpha-helical content and exhibited a longer Tyr lifetime, indicative of secondary and tertiary structural differences from isoform II. Isoforms I and II both had two fatty acid or fatty acyl CoA binding sites. Ligand binding decreased the isoform hydrodynamic radii by 3-4 A and increased Tyr rotational motions in a more restricted range. Fatty acyl CoAs were more effective than fatty acids in altering the isoform structures. Scatchard analysis showed that both isoforms bound cis- parinaric acid with high affinity (Kd values 41 and 60 nM, respectively) and bound trans-parinaric acid with 2- and 7-fold, respectively, higher affinity than for cis-parinaric acid. In contrast, isoform I had higher affinity for cis- and trans-parinaroyl CoAs (Kd values of 33 and 14 nM) than did isoform II (Kd values of 110 and 97 nM), thereby resulting in biphasic plots of parinaroyl-CoA binding to native L-FABP. Finally, displacement studies indicated that each isoform displayed distinct specificities for fatty acid/fatty acyl CoA chain length and unsaturation. Thus, rat L-FABP isoforms differ markedly in both structure and ligand binding function.

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Review: The liver bile acid‐binding proteins

Monaco¹

2009

Biopolymers

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The liver bile acid-binding proteins, L-BABPs, formerly called the liver "basic" fatty acid-binding proteins, are a subfamily of the fatty acid-binding proteins, FABPs. All the members of this protein group share the same fold: a 10 stranded beta barrel in which two short helices are inserted in between the first and the second strand of antiparallel beta sheet. The barrel encloses the ligand binding cavity of the protein while the two helices are believed to be involved in ligand accessibility to the binding site. The L-BABP subfamily has been found to be present in the liver of several vertebrates: fish, amphibians, reptiles, and birds but not in mammals. The members of the FABP family present in mammals that appear to be more closely related to the L-BABPs are the liver FABPs and the ileal BABPs, both very extensively studied. Several L-BABP X-ray structures are available and chicken L-BABP has also been studied using NMR spectroscopy. The stoichiometry of ligand binding for bile acids, first determined by X-ray crystallography for the chicken liver protein, is of two cholates per protein molecule with the only exception of zebrafish L-BABP which, due to the presence of a disulfide bridge, has a stoichiometry of 1:1. The stoichiometry of ligand binding for fatty acids, determined with several different techniques, is 1:1. An unanswered question of great relevance is the identity of the protein that in mammals performs the function that in other vertebrates is carried out by the L-BABPS.

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Amino acid exchange and covalent modification by cysteine and glutathione explain isoforms of fatty acid-binding protein occurring in bovine liver

Cited by 42 publications

References 0 publications

Phytanic acid is ligand and transcriptional activator of murine liver fatty acid binding protein

Phytanic acid is ligand and transcriptional activator of murine liver fatty acid binding protein

Isoforms of Rat Liver Fatty Acid Binding Protein Differ in Structure and Affinity for Fatty Acids and Fatty Acyl CoAs

Review: The liver bile acid‐binding proteins

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