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Fatty acid-binding proteins of nervous tissue

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Abstract

Fatty acid-binding proteins (FABPs) are cytosolic 14–15 kDa proteins, which are supposed to be involved in fatty acid (FA) uptake, transport, and targeting. They may modulate FA concentration and in this way influence function of enzymes, membranes, ion channels and receptors, and gene expression and cellular growth and differentiation. Nine FABP types can be discerned with a specific tissue distribution. In spite of 30–70% amino acid sequence identity, they have a similar tertiary, β-clam structure in which the FA is bound.

Nervous tissue contains four FABP types with a distinct spatio-temporal distribution. Myelin (M)-FABP is only present in the peripheral nerves, brain (B)-FABP and epidermal (E)-FABP mainly in glial cells and neurons, respectively of pre- and perinatal brain, and heart (H)-FABP in adult brain. Possible functions of FABPs in the nervous system are discussed.

Binding studies with a range of physiological FA showed no large differences between recombinant proteins of the four human FABP types in binding specificity and affinity, also not for polyunsaturated FA (PUFA). The transfer of FA from fixed liposomes to mitochondria was similarly promoted by the four types. A marked difference in conformational stability was observed with H-FABP > B-FABP > M-FABP > E-FABP. Surface epitopes of H-FABP showed reaction with anti-B-FABP antibodies, but no other cross-reactivity of FABP type and heterologous antibodies was observed. The functional significance of the distinct spatio-temporal pattern of the four FABP types remains to be elucidated.

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References

  • Abumrad N., Coburn C., and Ibrahimi A. (1999) Membrane proteins implicated in long-chain fatty acid uptake by mammalian cells: CD36, FATP and FABPm. Biochim. Biophys. Acta 1441, 4–13.

    PubMed  CAS  Google Scholar 

  • Allen G. W., Liu J-W., and De León M. (2000) Depletion of a fatty acid-binding protein impaires neurite outgrowth in PC12 cells. Mol. Brain Res. 76, 315–324.

    Article  PubMed  CAS  Google Scholar 

  • Banaszak L., Winter N., Xu Z., Bernlohr D. A., Cowan S., and Jones, T. A. (1994) Lipid-binding proteins: a family of fatty acid and retinoid transport proteins. Adv. Prot. Chem. 45, 89–151.

    Article  CAS  Google Scholar 

  • Bass N. M., Raghupathy E., Rhoads D. E., Manning J. A., and Ockner R. K. (1984) Partial purification of molecular weight 12000 fatty acid binding proteins from rat brain and their effect on synaptosomal Na+-dependent amino acid uptake. Biochemistry 23, 6539–6544.

    Article  PubMed  CAS  Google Scholar 

  • Bennett E., Stenvers K. L, Lund P. K., and Popko B. (1994) Cloning and characterization of a cDNA encoding a novel fatty acid binding protein from rat brain. J. Neurochem. 63, 1616–1624.

    Article  PubMed  CAS  Google Scholar 

  • Bernlohr D. A., Simpson M. A., Vogel Hertzel A., and Banaszak L. J. (1997) Intracellular lipid-binding proteins and their genes. Annu. Rev. Nutr. 17, 277–303.

    Article  PubMed  CAS  Google Scholar 

  • De León M., Welcher A. A., Liu N. Y., Ruda M. A., Shooter E. M., and Molina C. A. (1996) Fatty acid binding protein is induced in neurons of the dorsal root ganglia after peripheral nerve injury. J. Neurosci. Res. 44, 283–292.

    Article  PubMed  Google Scholar 

  • Desvergne B., Ijpenberg A., Devchand P. R., and Wahli W. (1998) The peroxisome proliferator-activated receptors at the cross-road of diet and hormonal signalling. J. Steroid Biochem. Mol. Biol. 65, 65–74.

    Article  PubMed  CAS  Google Scholar 

  • Eylar E. H., Szymanska I., Ishaque A., Ramwani J., and Dubiski S. (1980) Localization of the P2 protein in peripheral nerve myelin. J. Immunol. 124, 1086–1092.

    PubMed  CAS  Google Scholar 

  • Faroqui J. Z., Robb E., Boyce S. T., Warde G. D., and Nordlund J. J. (1995) Isolation of a unique melanogenic inhibitor from human skin xenografts: initial in vitro and in vivo characterization. J. Invest. Dermatol. 104, 739–743.

    Article  Google Scholar 

  • Feng L., Hatten M. E., and Heintz N. (1994) Brain lipid-binding protein (BLBP): a novel signaling system in the developing mammalian CNS. Neuron 12, 895–908.

    Article  PubMed  CAS  Google Scholar 

  • Feng L. and Heintz N. (1995) Differentiating neurons activate transcription of the brain lipid-binding protein gene in radial glia through a novel regulatory element. Development 121, 1719–1730.

    PubMed  CAS  Google Scholar 

  • Glatz J. F. C. and van der Vusse G. J. (1996) Cellular fatty acid-binding proteins: their function and physiological significance. Prog. Lipid Res. 35, 243–282.

    Article  PubMed  CAS  Google Scholar 

  • Godbout R., Marusyk H., Bisgrove D., Dabbagh L., and Poppema S. (1995) Localization of a fatty acid binding protein and its transcript in the developing chick retina. Exp. Eye Res. 60, 645–657.

    Article  PubMed  CAS  Google Scholar 

  • Godbout R., Bisgrove D. A., Shkolny D., and Day R. S. (1998) Correlation of B-FABP and GFAP expression in malignant glioma. Oncogene 16, 1955–1962.

    Article  PubMed  CAS  Google Scholar 

  • Green P., Glozman S., Kamensky B., and Yavin E. (1999) Developmental changes in rat brain membrane lipids and fatty acids: the preferential prenatal accumulation of docosaheaenoic acid. J. Lipid Res. 40, 960–966.

    PubMed  CAS  Google Scholar 

  • Grimaldi P. A., Teboul L., Gaillard D., Armengod A. V., and Amri E. Z. (1999) Long chain fatty acids as modulators of gene transcription in preadipose cells. Mol. Cell. Biochem. 192, 63–68.

    Article  PubMed  CAS  Google Scholar 

  • Hamilton J.A. and Kamp F. (1999) How are free fatty acids transported in membranes? Is it by proteins or by free diffusion through the lipids? Diabetes 48, 2255–2269.

    Article  PubMed  CAS  Google Scholar 

  • Heuckeroth R. O, Birkenmeier E. H., Levin M. S., and Gordon J. I. (1987) Analysis of the tissue-specific expression, developmental regulation, and linkage relationships of a rodent gene encoding heart fatty acid binding protein. J. Biol. Chem. 262, 9709–9717.

    PubMed  CAS  Google Scholar 

  • Hohoff C. and Spener F. (1998) Fatty acid binding proteins and mammary-derived growth inhibitor. Fett (Lipid) 6, 252–263.

    Article  Google Scholar 

  • Hohoff C., Börchers T., Rüstow B., Spener F., and van Tilbeurgh H. (1999) Expression, purification, and crystal structure determination of recombinant human epidermal-type fatty acid binding protein. Biochemistry 38, 12,229–12,239.

    Article  CAS  Google Scholar 

  • Huynh H. T., Larsson C., Narod S., and Pollak M. (1995) Tumor suppressor activity of the gene encoding mammary-derived growth inhibitor. Cancer Res. 55, 2225–2231.

    PubMed  CAS  Google Scholar 

  • Jump D. B. and Clarke S. D. (1999) Regulation of gene expression by dietary fat. Annu. Rev. Nutr. 19, 63–90.

    Article  PubMed  CAS  Google Scholar 

  • Kane C. D., Ribarik Coe N., Vanlandingham B., Krieg P., and Bernlohr D. A. (1996) Expression, purification, and ligand-binding analysis of recombinant keratinocyte lipid-binding protein (MAL-1), an intracellular lipid-binding protein found overexpressed in neoplastic skin cells. Biochemistry 35, 2895–2900.

    Google Scholar 

  • Keler T. and Sorof S. (1993) Growth promotion of transfected hepatoma cells by liver fatty acid binding protein. J. Cell. Physiol. 157, 33–40.

    Article  PubMed  CAS  Google Scholar 

  • Kingma P., Bok D., and Ong D. E. (1998) Bovine epidermal fatty acid-binding protein: determination of ligand specificity and cellular localization in retina and testis. Biochemistry 37, 3250–3257.

    Article  PubMed  CAS  Google Scholar 

  • Kurtz A., Zimmer A., Schnütgen F., Brüning G., Spener F., and Müller T. (1994) The expression pattern of a novel gene encoding brain-fatty acid binding protein correlates with neuronal and glial cell development. Development 120, 2637–2649.

    PubMed  CAS  Google Scholar 

  • Liu Y., Molina C. A., Welcher A. A., Longo L. D., and De León M. (1997) Expression of DA11, a neuronal-injury-induced fatty acid binding protein, coincides with axon growth and neuronal differentiation during central nervous system development. J. Neurosci. Res. 48, 551–562.

    Article  PubMed  CAS  Google Scholar 

  • Liu Y., Longo L. D., and De León M. (2000) In situ and immunocytochemical localization of E-FABP mRNA and protein during neuronal migration and differentiation in the rat brain. Brain Res. 852, 16–27.

    Article  PubMed  CAS  Google Scholar 

  • Maatman R. G. H. J., van Moerkerk H. T. B., Nooren I. M. A., van Zoelen E. J. J., and Veerkamp J. H. (1994) Expression of human liver fatty acid-binding protein in Escherichia coli and comparative analysis of its binding characteristics with muscle fatty acid-binding protein. Biochim. Biophys. Acta 1214, 1–10.

    PubMed  CAS  Google Scholar 

  • Martin G., Schoonjans K., Lefebvre A., Staels B., and Auwerx J. (1997) Coordinate regulation of the expression of the fatty aid transport protein and acyl-CoA synthetase genes by PPARα and PPARγ activators. J. Biol. Chem. 272, 28,210–28,217.

    CAS  Google Scholar 

  • Masouyé I., Hagens G., van Kuppevelt T. H., Madsen P., Saurat J-H., Veerkamp J. H., et al. (1997) Endothelial cells of the human microvasculature express epidermal fatty acid-binding protein. Circ. Res. 81, 297–303.

    PubMed  Google Scholar 

  • Narayanan V., Barbosa E., Reed R., and Tennekoon G. (1988) Characterization of a cloned cDNA encoding rabbit myelin P2 protein. J. Biol. Chem. 263, 8322–8337.

    Google Scholar 

  • Nunez E. A. (1997) Fatty acids involved in signal crosstalk between cell membrane and nucleus. Prostaglandins Leukot. Essent. Fatty Acids 57, 429–434.

    Article  CAS  Google Scholar 

  • Owada Y., Yoshimoto T., and Kondo H. (1996a) Spatiotemporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains. J. Chem. Neuroanat. 12, 113–122.

    Article  PubMed  CAS  Google Scholar 

  • Owada Y., Yoshimoto T., and Kondo H. (1996b) Increased expression of the mRNA for brain- and skin-type but not heart-type fatty acid binding proteins following kainic acid systemic administration in the hippocampal glia of adult rats. Mol. Brain Res. 42, 156–160.

    Article  PubMed  CAS  Google Scholar 

  • Owada Y., Utsunomiya A., Yoshimoto T., and Kondo H. (1997) Changes in gene expression for skin-type fatty acid binding protein in hypoglossal motor neurons following nerve crush. Neurosci. Letters 223, 25–28.

    Article  CAS  Google Scholar 

  • Paulussen R. J. A., Geelen M. J. H., Beynen A. C., and Veerkamp J. H. (1989) Immunochemical quantitation of fatty-acid-binding proteins. I. Tissue and intracellular distribution, postnatal development and influence of physiological conditions on rat heart and liver FABP. Biochim. Biophys. Acta 1001, 201–209.

    PubMed  CAS  Google Scholar 

  • Prinsen C. F. M. and Veerkamp J. H. (1998) Transfection of L6 myoblasts with adipocyte fatty acid-binding protein cDNA does not affect fatty acid uptake but disturbs lipid metabolism and fusion. Biochem. J. 329, 265–273.

    PubMed  CAS  Google Scholar 

  • Ribarik Coe N. and Bernlohr D. A. (1998) Physiological properties and functions of intracellular fatty acid-binding proteins. Biochim. Biophys. Acta 1391, 287–306.

    Google Scholar 

  • Richieri G. V. and Kleinfeld A. M. (1995) Unbound free fatty acid levels in human serum. J. Lipid Res. 36, 229–240.

    PubMed  CAS  Google Scholar 

  • Richieri G. V., Ogata R. T., and Kleinfeld A. M. (1994) Equilibrium constants for the binding of fatty acids with fatty acid-binding proteins from adipocyte, intestine, heart, and liver measured with the fluorescent probe ADIFAB. J. Biol. Chem. 269, 23,918–23,930.

    CAS  Google Scholar 

  • Richieri G. V., Ogata R. T., and Kleinfeld A. M. (1999) The measurement of free fatty acid concentration with the fluorescent probe ADIFAB: a practical guide for the use of the ADIFAB probe. Mol. Cell. Biochem. 192, 87–94.

    Article  PubMed  CAS  Google Scholar 

  • Richieri G. V., Ogata R. T., Zimmerman A. W., Veerkamp J. H., and Kleinfeld A. M. (2000) Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions. Biochemistry (in press).

  • Rolf B., Oudenampsen-Krüger E., Börchers T., Færgeman N. J., Knudsen J., Lezius A., and Spener F. (1995) Analysis of the ligand binding properties of recombinant bovine liver-type fatty acid binding protein. Biochim. Biophys. Acta 1259, 245–253.

    PubMed  Google Scholar 

  • Schnütgen F., Börchers T., Müller T., and Spener F. (1996) Heterologous expression and characterization of mouse brain fatty acid binding protein. Biol. Chem. Hoppe-Seyler 377, 211–215.

    PubMed  Google Scholar 

  • Schoentgen F., Pignède G., Bonanno L. M., and Jollès P. (1989) Fatty acid-binding protein from bovine brain. Amino acid sequence and some properties. Eur. J. Biochem. 185, 35–40.

    Article  PubMed  CAS  Google Scholar 

  • Schoonjans K., Staels B., and Auwerx J. (1996) The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochim. Biophys. Acta 1302, 93–109.

    PubMed  CAS  Google Scholar 

  • Sellner P. A., Chu W., Glatz J. F. C., and Berman N. E. J. (1995) Developmental role of fatty acid-binding proteins in mouse brain. Dev. Brain Res. 89, 33–46.

    Article  CAS  Google Scholar 

  • Senjo M., Ishibashi T., Imai Y., Takahashi K., and Ono T. (1985) Isolation and characterization of fatty acid-binding protein from rat brain. Arch. Biochem. Biophys. 236, 662–668.

    Article  PubMed  CAS  Google Scholar 

  • Specht B., Bartetzko N., Hohoff C., Kuhl H., Franke R., Börchers T., and Spener F. (1996) Mammary derived growth inhibitor is not a distinct protein but a mix of heart-type and adipocyte-type fatty acid-binding protein. J. Biol. Chem. 271, 19,943–19,949.

    CAS  Google Scholar 

  • Thompson J., Ory J., Reese-Wagoner A., and Banaszak L. (1999) The liver fatty acid binding protein — comparison of cavity properties of intracellular lipid-binding proteins. Mol. Cell. Biochem. 192, 9–16.

    Article  PubMed  CAS  Google Scholar 

  • Trapp B. D., Dubois-Dalcq M., and Quarles R. H. (1984) Ultrastructural localization of P2 protein in actively myelinating rat Schwann cells. J. Neurobiochem. 43, 944–948.

    Article  CAS  Google Scholar 

  • Utsonomiya A., Owada Y., Yoshimoto T., and Kondo H. (1997) Localization of mRNA for fatty acid transport protein in developing and mature brain of rats. Mol. Brain Res. 46, 217–222.

    Article  Google Scholar 

  • Veerkamp J. H. (1995) Fatty acid transport and fatty acid-binding proteins. Proc. Nutr. Soc. 54, 23–37.

    Article  PubMed  CAS  Google Scholar 

  • Veerkamp J. H., van Moerkerk H. T. B., Glatz J. F. C., and van Hinsbergh V. W. M. (1983) Incomplete palmitate oxidation in cell-free systems of rat and human muscles. Biochim. Biophys. Acta 753, 399–410.

    PubMed  CAS  Google Scholar 

  • Veerkamp J. H. and Maatman R. G. H. J. (1995) Cytoplasmic fatty acid-binding proteins: their structure and genes. Prog. Lipid Res. 34, 17–52.

    Article  PubMed  CAS  Google Scholar 

  • Veerkamp J. H., Peeters R. A., and Maatman R. G. H. J. (1991) Structural and functional features of different types of cytoplasmic fatty acid-binding proteins. Biochim. Biophys. Acta 1081, 1–24.

    PubMed  CAS  Google Scholar 

  • Veerkamp J. H., van Kuppevelt T. H. M. S. M., Maatman R. G. H. J., and Prinsen C. F. M. (1993) Structural and functional aspects of cytosolic fatty acid-binding proteins. Prostaglandins Leukot. Essent. Fatty Acids 49, 887–906.

    Article  PubMed  CAS  Google Scholar 

  • Veerkamp J. H., van Moerkerk H. T. B., Prinsen C. F. M., and van Kuppevelt T. H. (1999) Structural and functional studies on different human FABP types. Mol. Cell. Biochem. 192, 137–142.

    Article  PubMed  CAS  Google Scholar 

  • Walz D. A., Wider M. D., Snow J. W., Dass C., and Desiderio D. M. (1988) The complete amino acid sequence of procine gastrotropin, an ileal protein which simulates gastricacid and pepsinogen secretion. J. Biol. Chem. 263, 14,189–14,195.

    CAS  Google Scholar 

  • Weisiger R. A. (1996) Cytoplasmic transport of lipids: role of binding proteins. Comp. Biochem. Physiol. 115B, 319–331.

    CAS  Google Scholar 

  • Xu L. Z., Sanchez R., Sali A., and Heintz N. (1996) Ligand specificity of brain lipid-binding protein. J. Biol. Chem. 271, 24,711–24,719.

    CAS  Google Scholar 

  • Young J. K., Baker J. H., and Müller T. (1996) Immunoreactivity for brain-fatty acid binding protein in Gomoripositive astrocytes. Glia 16, 218–226.

    Article  PubMed  CAS  Google Scholar 

  • Zanotti G. (1999) Muscle fatty acid-binding protein. Biochim. Biophys. Acta 1441, 94–105.

    PubMed  CAS  Google Scholar 

  • Zimmerman A. W. and Veerkamp J. H. (1998) Members of the fatty acid-binding protein family inhibit cell-free protein synthesis. FEBS Let. 437, 183–186.

    Article  CAS  Google Scholar 

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Veerkamp, J.H., Zimmerman, A.W. Fatty acid-binding proteins of nervous tissue. J Mol Neurosci 16, 133–142 (2001). https://doi.org/10.1385/JMN:16:2-3:133

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