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Cytochrome P450, peroxisome proliferation, and cytoplasmic fatty acid-binding protein content in liver, heart and kidney of the diabetic rat

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Abstract

Diabetes mellitus generally results in an increased systemic fatty acid mobilization which can be associated with an increase in mitochondrial and peroxisomal β-oxidation of fatty acids in selected tissues. The latter is usually accompanied by a concomitant increase in the tissue content of cytoplasmic fatty acid-binding protein (FABP) which functions in the intracellular translocation of fatty acids. It was previously found that in liver clofibrate-induced proliferation of peroxisomes and increase in FABP expression each are dependent on the induction by cytochrome P4504A1 -mediated (CYP4A1) formation of dicarboxylic acids. We studied whether peroxisome proliferation and an increase of FABP contents in liver, heart and kidney of streptozotocin-induced diabetic rats are also accompanied by an increase of CYP4A1 activity, as this would indicate a possible regulatory role for dicarboxylic acids in peroxisome proliferation and FABP induction in diabetic organs other than liver. In livers of the diabetic rat, a concomitant increase was observed of the activities of CYP4A1 and the peroxisomal key enzyme fatty acyl-CoA oxidase (FACO) and of the FABP content. In the diabetic heart FACO activity and FABSP content also increased, but there was no induction of CYP4A1 activity. Conversely, in diabetic kidney there was no increase in FACO activity nor FABP content in spite of a marked induction of CYP4A1 activity. It is concluded that streptozotocin-induced diabetes leads to increased peroxisome proliferation and increased levels of FABP in both liver and heart, which only in liver is accompanied by an induction of the cytochrome P450 system. Consequently, it is not likely that dicarboxylic acids are involved in the induction of peroxisome proliferation in the heart.

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References

  1. DeFronzo RA: Pathogenesis of type 2 (non-insulin dependent) diabetes mellitus: A balanced overview. Diabetologica 35: 389–397, 1992

    Google Scholar 

  2. Mannaerts GP, van Veldhoven PP: Role of peroxisomes in mammalian metabolism. Cell Biochem Funct 10: 141–151, 1992

    Google Scholar 

  3. Lock EA, Mitchell AM, Elcombe CR: Biochemical mechanisms of induction of hepatic peroxisome proliferation. Annu Rev Pharmacol Toxicol 29: 145–163, 1989

    Google Scholar 

  4. Vamecq J, Draye JP: Peroxisomal and mitochondrial beta-oxidation of monocarboxyl-CoA, omega-hydroxymonocarboxyl-CoA and dicarboxyl-CoA esters in tissues from untreated and clofibrate-treated rats. J Biochem 106: 216–222, 1989

    Google Scholar 

  5. Osmundsen H, Bremer J, Pedersen J1. Metabolic aspects of peroxisomal β-oxidation. Biochim Biophys Acta 1085: 141–158, 1991

    Google Scholar 

  6. Reddy JK, Mannaerts GP: Peroxisomal lipid metabolism. Annu Rev Nutr 14: 343–370, 1994

    Google Scholar 

  7. Issemann I, Prince R, Tugwood J, Green S: A role for fatty acids and liver fatty acid binding protein in peroxisome proliferation? Biochem Soc Trans 20: 824–827, 1992

    Google Scholar 

  8. Glatz JFC, van der Vusse GJ: Cellular fatty acid-binding proteins: their function and physiological significance. Progr Lipid Res 35: 243–282, 1996

    Google Scholar 

  9. Kaikaus RM, Sui Z, Lysenko N, et al.: Regulation of pathways of extramitochondrial fatty acid oxidation and liver fatty acid-binding protein by long-chain monocarboxylic fatty acids in hepatocytes. Effect of inhibition of carnitine palmitoyltransferase 1. J Biol Chem 268: 26866–26871, 1993

    Google Scholar 

  10. Mortensen PB: Formation and degradation of dicarboxylic acids in relation to alterations in fatty acid oxidation in rats. Biochim Biophys Acta 1124: 71–79, 1992

    Google Scholar 

  11. Isseman I, Green S: Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347: 645–650, 1990

    Google Scholar 

  12. Beck F, Plummer S, Senior PV, Byrne S, Green S, Brammar W: The ontogeny of peroxisome-proliferator-activated receptor gene expression in the mouse and rat. Proc R Soc Lond B 247: 83–87, 1992

    Google Scholar 

  13. Mangelsdorf DJ, Thummel C, Beato M, et al.: The nuclear receptor superfamily: The second decade. Cell 83: 835–839, 1995

    Google Scholar 

  14. Osmundsen H, Brodal B, Hovik R: A luminometric assay for peroxisomal β-oxidation. Effects of fasting and streptozotocin-diabetes on β-oxidation. Biochern J 260: 215–220, 1989

    Google Scholar 

  15. Kozuka H, Watanabe T, Horie S, Yamada J, Suga T, Ikeda T: Characteristics of peroxisome proliferation: Co-induction of peroxisomal fatty acid oxidation-related enzymes with microsomal laurate hydroxyiase. Chem Pharm Bull Tokyo 39: 1267–1271, 1991

    Google Scholar 

  16. Xu L, Ash M, Abdelaleern S, Lowe JE, Badr M: Hyperinsulinemia inhibits hepatic peroxisomal beta-oxidation in rats. Horm Metab Res 27: 76–78, 1995

    Google Scholar 

  17. Gustafsson J-Å, Gearing K, Widmark E, et al.: Effects of fatty acids on gene expression mediated by a member of the nuclear receptor supergene family. Prog Clin Biol Res 387: 21–28, 1994

    Google Scholar 

  18. Kaikaus RM, Chan WK, Lysenko N, Ray R, Ortiz de Montellano PR, Bass NM: Induction of peroxisomal fatty acid beta-oxidation and liver fatty acid-binding protein by peroxisome proliferators-mediation via the cytochrome P-45OlVA1 omega-Hydroxylase pathway. J Biol Chem 268: 9593–9603, 1993

    Google Scholar 

  19. Kaikaus RM, Chan WK, Ortiz de Montellano PR, Bass NM: Mechanisms of regulation of liver fatty acid-binding protein. Mol Cell iochem 123: 93–100, 1993

    Google Scholar 

  20. Shimojo N, Ishizaki T, Imaoka S, Funae Y, Fujii S, Okuda K: Changes in amounts of cytochrome-P450 isozymes and levels of catalytic activities in hepatic and renal microsomes of rats with streptozocin-induced diabetes. Biochem Pharmacol 46: 621–627, 1993

    Google Scholar 

  21. Glatz JFC, van Breda E, Keizer HA, et al.: Rat heart fatty acid-binding protein content is increased in experimental diabetes. Biochem Biophys Res Commun 199: 639–646, 1994

    Google Scholar 

  22. McCallum GIP, Horton JE, Faikner KC, Bend JR: Microsomal Cytochrome-P450 1A1 dependent monooxygenase activity in guinea pig heart - induction, inhibition, and increased activity by addition of exogenous NADPH Cytochrome-P450 reductase. Can J Physiol Pharmacol 71: 151–156, 1993

    Google Scholar 

  23. Rutten AAJJL, Falke HE, Catsburg JF, et al.: Interlaboratory comparison of total cytochrome P-450 and protein determination in rat liver microsomes. Reinvestigation of assay conditions. Arch Toxicol 61: 27–33, 1987

    Google Scholar 

  24. Vannecq J: Fluorometric assay of peroxisomal oxidases. Anal Biochem 186: 340–349, 1990

    Google Scholar 

  25. Mannaerts GP, van Veldhoven P, van Broekhoven A, Vandebroek G, Debeer LJ: Evidence that peroxisomal acyl-CoA synthetase is located at the cytoplasmic side of the peroxisomal membrane. Biochem J 204: 17–23, 1982

    Google Scholar 

  26. Vork MM, Glatz JFC, Surtel DA, Knubben HJ, van der Vusse GJ: A sandwich enzyme linked immuno-sorbent assay for the determination of rat heart fatty acid-binding protein using the streptavidin-biotin system. Application to tissue and effluent samples from normoxic rat heart perfusion. Biochim Biophys Acta 1075: 199–205, 1991

    Google Scholar 

  27. Van Nieuwenhoven FA, Verstijnen CPHJ, van Eys GJJM, et al.: Fatty acid transfer across the myocardial capillary wall: No evidence of a substantial role for cytoplasmic fatty acid binding protein. J Mol Cell Cardiol 26: 1635–1647, 1994

    Google Scholar 

  28. Onnura T, Sato R. The carbon monoxide-binding pigment of liver microsomes. II. Solubilization, purification, and properties. J Biol Chem 239: 2379–2385, 1964

    Google Scholar 

  29. Stegeman JJ, Woodin BR, Klotz AV, Wolke RE, Orme-Johnson NR: Cytochrome P-450 and monooxygenase activity in cardiac microsomes from fish Stenotomus chrysops. Mol Pharmacol 21: 517–526, 1982

    Google Scholar 

  30. Engels W, Kamps MA, Lemmens PJ, van der Vusse GJ, Reneman RS: Determination of prostaglandins and thromboxane in whole blood by high-performance liquid chromatography with fluorimetric detection. J Chromatogr 427: 209–218, 1988

    Google Scholar 

  31. Reinke LA, Moyer MJ: p-Nitrophenol hydroxylation: A microsomal oxidation which is highly induceble by ethanol. Drug Metab Dispos 13: 548–552, 1985

    Google Scholar 

  32. Wallenstein S, Zucker C, Fleiss JL: Some statistical methods useful in circulation research. Circ Res 47: 1–9, 1980

    Google Scholar 

  33. Seyer-Hansen K. Renal hyperthrophy in experimental diabetes. Kidney Int 23: 643–646, 1983

    Google Scholar 

  34. Maatman RG, van de Westerlo EM, van Kuppevelt TH, Veerkamp JH: Molecular identification of the liver-and the heart-type fatty acid-binding proteins in human and rat kidney. Use of the reverse transcriptase polymerase chain reaction. Biochem J 288: 285–290, 1992

    Google Scholar 

  35. Abraham NG, Pinto A, Levere RD, Mullane K: Identification of heme oxygenase and cytochrome P-450 in the rabbit heart. J Mol Cell Cardiol 19: 73–81, 1987

    Google Scholar 

  36. Gottlicher M, Widmark E, Li Q, Gustafsson JA: Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc Nati Acad Sci USA 89: 4653–4657, 1992

    Google Scholar 

  37. Göttlicher M, Demoz A, Svensson D, Tollet P, Berge RK, Gustafsson JA: Structural and metabolic requirements for activators of the peroxisome Proliferator-Activated receptor. Biochem Pharmacol 46: 2177–2184, 1993

    Google Scholar 

  38. Barnett CR, Flatt PR, Ioannides C: Modulation of the rat hepatic cytochrome p450 composition by long-term streptozotocin-induced insulin-dependent diabetes. J Biochem Toxicol 9: 63–69, 1994

    Google Scholar 

  39. Shimojo N: Cytochrome P450 changes in rats with streptozocin-induced diabetes. Int J Biochern 26: 1261–1268, 1994

    Google Scholar 

  40. Veerkamp JH, van Moerkerk HTB, van den Born J: No correlation between changes in fatty-acid binding content and fatty acid oxidation capacity of rat tissues in experimental diabetes. Int J Biochem Cell Biol 28: 473–478, 1996

    Google Scholar 

  41. Asayama K, Yokota S, Kato K. Peroxisomal oxidases in various tissues of diabetic rats. Diabetes Res Clin Pract 11: 89–94, 1991

    Google Scholar 

  42. Yokota S, Asayama K: Proliferation of myocardial peroxisomes in experimental rat diabetes: A biochemical and immunocytochemical study. Virchows Arch B 63: 43–69, 1992

    Google Scholar 

  43. Chu C, Mao L-F, Schultz H: Estimation of peroxisomal β-oxidation in rat heart by a direct assay of acyl-CoA oxidase. Biochem J 302: 23–29, 1994

    Google Scholar 

  44. Norseth J, Thomassen MS. Stimulation of microperoxisomal IS-oxidation in rat heart by high-fat diets. Biochim Biophys Acta 751: 312–320, 1983

    Google Scholar 

  45. van der Vusse GJ, Glatz JFC, Stam HCG, Reneman RS: Fatty acid homeostasis in the normoxic and ischemic heart. Physiol Rev 72: 881–940, 1992

    Google Scholar 

  46. Guengerich FP, Mason PS: Immunological comparison of hepatic and extrahepatic cytochromes P-450. Mol Pharmacol 15: 154–164, 1979

    Google Scholar 

  47. Nelson DR, Kamataki T, Waxman DJ, et al.: The P450 superfamily: Update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol 12: 1–51, 1993

    Google Scholar 

  48. Porter TD, Coon MJ: Cytochrome P-450. Multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms. J Biol Chem 266: 13469–13472, 1991

    Google Scholar 

  49. Wu S, Moomaw CR, Tomer KB, Faick JR, Zeldin DC: Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart. J Biol Chem 271: 3460–3468, 1996

    Google Scholar 

  50. McGiff JC, Quilley CP, Carroll MA: The contribution of cytochrome P450–dependent arachidonate metabolites to integrated renal function. Steroids 58: 573–579, 1993

    Google Scholar 

  51. Decraemer D, Vamecq J, Roels F, Vallee IL, Pauwels M, Vandenbranden C: Peroxisomes in liver, heart, and kidney of mice fed a commercial fish oil preparation: Original data and review on peroxisomal changes induced by high-fat diets. J Lipid Res 35: 1241–1250, 1994

    Google Scholar 

  52. Asayama K, Okada Y, Kato K: Peroxisomal beta-oxidation in liver and muscles of gold-thioglucose-induced obese mice: Correlation with body weight. Int J Obes 15: 45–49, 1991

    Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

    Wim Engels & Bruce H.R. Wolffenbuttel

  2. Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

    Marc van Bilsen, Ger J. van der Vusse & Jan F.C. Glatz

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  1. Wim Engels
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  2. Marc van Bilsen
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  3. Bruce H.R. Wolffenbuttel
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  4. Ger J. van der Vusse
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  5. Jan F.C. Glatz
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Engels, W., van Bilsen, M., Wolffenbuttel, B.H. et al. Cytochrome P450, peroxisome proliferation, and cytoplasmic fatty acid-binding protein content in liver, heart and kidney of the diabetic rat. Mol Cell Biochem 192, 53–61 (1999). https://doi.org/10.1023/A:1006855214237

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