Peroxisomes in cardiomyocytes and the peroxisome / peroxisome proliferator-activated receptor-loop

Claudia Colasante; Jiangping Chen; Barbara Ahlemeyer; Eveline Baumgart-Vogt

doi:10.1160/TH14-06-0497

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2015; 113(03): 452-463
DOI: 10.1160/TH14-06-0497

Theme Issue Article

Schattauer GmbH

Peroxisomes in cardiomyocytes and the peroxisome / peroxisome proliferator-activated receptor-loop

Claudia Colasante

¹Institute for Anatomy and Cell Biology II, Division of Medical Cell Biology, University of Giessen, Giessen, Germany

,

Jiangping Chen

¹Institute for Anatomy and Cell Biology II, Division of Medical Cell Biology, University of Giessen, Giessen, Germany

,

Barbara Ahlemeyer

¹Institute for Anatomy and Cell Biology II, Division of Medical Cell Biology, University of Giessen, Giessen, Germany

,

Eveline Baumgart-Vogt

¹Institute for Anatomy and Cell Biology II, Division of Medical Cell Biology, University of Giessen, Giessen, Germany

› Institutsangaben

Abstract

Summary

It is well established that the heart is strongly dependent on fatty acid metabolism. In cardiomyocytes there are two distinct sites for the β-oxidisation of fatty acids: the mitochondrion and the peroxisome. Although the metabolism of these two organelles is believed to be tightly coupled, the nature of this relationship has not been fully investigated. Recent research has established the significant contribution of mitochondrial function to cardiac ATP production under normal and pathological conditions. In contrast, limited information is available on peroxisomal function in the heart. This is despite these organelles harbouring metabolic pathways that are potentially cardioprotective, and findings that patients with peroxisomal diseases, such as adult Refsum’s disease, can develop heart failure. In this article, we provide a comprehensive overview on the current knowledge of peroxisomes and the regulation of lipid metabolism by PPARs in cardiomyocytes. We also present new experimental evidence on the differential expression of peroxisome-related genes in the heart chambers and demonstrate that even a mild peroxisomal biogenesis defect (Pex11α^-/- ) can induce profound alterations in the cardiomyocyte’s peroxisomal compartment and related gene expression, including the concomitant deregulation of specific PPARs. The possible impact of peroxisomal dysfunction in the heart is discussed and a model for the modulation of myocardial metabolism via a peroxisome/PPAR-loop is proposed.

Keywords

Peroxisome - β-oxidation of fatty acids - peroxisome proliferatoractivated receptor - heart failure - peroxisomal disorders

Volltext

Referenzen

References
1 Kehat I, Molkentin JD. Molecular pathways underlying cardiac remodeling during pathophysiological stimulation. Circulation 2010; 122: 2727-2735.
2 Abel ED. et al. Cardiac remodeling in obesity. Physiol Rev 2008; 88: 389-419.
3 Lopaschuk GD. et al. Myocardial fatty acid metabolism in health and disease. Physiol Rev 2010; 90: 207-258.
4 Holloway GP. et al. In obese Zucker rats, lipids accumulate in the heart despite normal mitochondrial content, morphology and long-chain fatty acid oxidation. J Physiol 2011; 589: 169-180.
5 Guzzardi MA, Iozzo P. Fatty heart, cardiac damage, and inflammation. Rev Dia-bet Stud 2011; 8: 403-417.
6 Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation 2007; 115: 3213-3223.
7 Shen X, Zheng S, Metreveli NS. et al. Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy. Diabetes 2006; 55: 798-805.
8 Ye G. et al. Catalase protects cardiomyocyte function in models of type 1 and type 2 diabetes. Diabetes 2004; 53: 1336-1343.
9 Rhodin J. Correlation of ultrastructural organisation and function in normal and 1245 experimentally changed proximal convoluted tubule cells of the mouse kidney. Doctoral Thesis, Karolinska Institutet, Aktiebolaget Godvil,; Stockholm.: 1954
10 Gänsler H, Rouiller C. Modification physiologiques et pathologiques du chon-driome. Schweiz Z Allg Pathol Bakt 1956; 19: 217-243.
11 Baumgart E. Application of in situ hybridisation, cytochemical and immunocy-tochemical techniques for the investigation of peroxisomes. A review including novel data. Robert Feulgen Prize Lecture 1997. Histochem Cell Biol 1997; 108: 185-210.
12 De Duve C, Baudhuin P. Peroxisomes (microbodies and related particles). Physiol Rev 1966; 46: 323-357.
13 Baudhuin P. et al. Combined biochemical and morphological study of particu-late fractions from rat liver. Analysis of preparations enriched in lysosomes or in particles containing urate oxidase, D-amino acid oxidase, and catalase. J Cell Biol 1965; 26: 219-243.
14 Wanders RJ, Waterham HR. Biochemistry of mammalian peroxisomes revisited. Annu Rev Biochem 2006; 75: 295-332.
15 Kovacs WJ. et al. Localisation of the pre-squalene segment of the isoprenoid bio-synthetic pathway in mammalian peroxisomes. Histochem Cell Biol 2007; 127: 273-290.
16 Distel B. et al. A unified nomenclature for peroxisome biogenesis factors. J Cell Biol 1996; 135: 1-3.
17 Fujiki Y. et al. Peroxisome biogenesis in mammalian cells. Front Physiol 2014; 5: 307.
18 Goldfischer S, Moore CL, Johnson AB. et al. Peroxisomal and mitochondrial defects in the cerebro-hepatorenal syndrome. Science 1973; 182: 62-64.
19 Wanders RJ, Waterham HR. Peroxisomal disorders I: biochemistry and genetics of peroxisome biogenesis disorders. Clin Genet 2005; 67: 107-133.
20 Monnens L, Heymans H. Peroxisomal disorders: clinical characterisation. J Inherit Metab Dis 1987; 10 (Suppl. 01) 23-32.
21 Van Veldhoven PP. Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism. J Lipid Res 2010; 51: 2863-2895.
22 Wanders RJ, Waterham HR. Peroxisomal disorders: the single peroxisomal enzyme deficiencies. Biochim Biophys Acta 2006; 1763: 1707-1720.
23 Yik WY. et al. Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders. Hum Mutat 2009; 30: E467-E480.
24 Koh JT. et al. Cardiac Characteristics of Transgenic Mice Overexpressing Refsum Disease Gene-Associated Protein within the Heart. Biochem Biophys Res Commun 2001; 286: 1107-1116.
25 Wanders RJ, Komen JC. Peroxisomes, Refsum’s disease and the alpha- and omega-oxidation of phytanic acid. Biochem Soc Trans 2007; 35: 865-869.
26 Grings M. et al. Phytanic acid disturbs mitochondrial homeostasis in heart of young rats: a possible pathomechanism of cardiomyopathy in Refsum disease. Mol Cell Biochem 2012; 366: 335-343.
27 Baes M. et al. A mouse model for Zellweger syndrome. Nat Genet 1997; 17: 49-57.
28 Faust PL, Hatten ME. Targeted deletion of the PEX2 peroxisome assembly gene in mice provides a model for Zellweger syndrome, a human neuronal migration disorder. J Cell Biol 1997; 139: 1293-1305.
29 Li X. et al. PEX11alpha is required for peroxisome proliferation in response to 4-phenylbutyrate but is dispensable for peroxisome proliferator-activated receptor alpha-mediated peroxisome proliferation. Mol Cell Biol 2002; 22: 8226-8240.
30 Li X. et al. PEX11 beta deficiency is lethal and impairs neuronal migration but does not abrogate peroxisome function. Mol Cell Biol 2002; 22: 4358-4365.
31 Maxwell M. et al. Pex13 inactivation in the mouse disrupts peroxisome biogenesis and leads to a Zellweger syndrome phenotype. Mol Cell Biol 2003; 23: 5947-5957.
32 Brites P. et al. Impaired neuronal migration and endochondral ossification in Pex7 knockout mice: a model for rhizomelic chondrodysplasia punctata. Hum Mol Genet 2003; 12: 2255-2267.
33 Fan CY. et al. Hepatocellular and hepatic peroxisomal alterations in mice with a disrupted peroxisomal fatty acyl-coenzyme A oxidase gene. J Biol Chem 1996; 271: 24698-24710.
34 Baes M. et al. Inactivation of the peroxisomal multifunctional protein-2 in mice impedes the degradation of not only 2-methyl-branched fatty acids and bile acid intermediates but also of very long chain fatty acids. J Biol Chem 2000; 275: 16329-16336.
35 Rodemer C. et al. Inactivation of ether lipid biosynthesis causes male infertility, defects in eye development and optic nerve hypoplasia in mice. Hum Mol Genet 2003; 12: 1881-1895.
36 Baumgart E. et al. Mitochondrial alterations caused by defective peroxisomal biogenesis in a mouse model for Zellweger syndrome (PEX5 knockout mouse). Am J Pathol 2001; 159: 1477-1494.
37 Trijbels JM. et al. Biochemical studies in the liver and muscle of patients with Zellweger syndrome. Pediatr Res 1983; 17: 514-517.
38 Monnig G. et al. Phytanic acid accumulation is associated with conduction delay and sudden cardiac death in sterol carrier protein-2/sterol carrier protein-x deficient mice. J Cardiovasc Electrophysiol 2004; 15: 1310-1316.
39 Seedorf U. et al. Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function. Genes Dev 1998; 12: 1189-1201.
40 da Silva TF. et al. The importance of ether-phospholipids: a view from the perspective of mouse models. Biochim Biophys Acta 2012; 1822: 1501-1508.
41 Braverman N. et al. A Pex7 hypomorphic mouse model for plasmalogen deficiency affecting the lens and skeleton. Mol Genet Metab 2010; 99: 408-416.
42 Braverman N. et al. Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata. Nat Genet 1997; 15: 369-376.
43 Ferdinandusse S. et al. Ataxia with loss of Purkinje cells in a mouse model for Refsum disease. Proc Natl Acad Sci USA 2008; 105: 17712-17717.
44 Fahimi HD, Baumgart E. Current cytochemical techniques for the investigation of peroxisomes. A review. J Histochem Cytochem 1999; 47: 1219-1232.
45 Hand AR. Letter: Peroxisomes (microbodies) in striated muscle cells. J Histochem Cytochem 1974; 22: 207-209.
46 Herzog V, Fahimi HD. Microbodies (peroxisomes) containing catalase in myocardium: morphological and biochemical evidence. Science 1974; 185: 271-273.
47 Hicks L, Fahimi HD. Peroxisomes (microbodies) in the myocardium of rodents and primates. A comparative Ultrastructural cytochemical study. Cell Tissue Res 1977; 175: 467-481.
48 Kvannes J. et al. The peroxisomal beta-oxidation enzyme system of rat heart. Basal level and effect of the peroxisome proliferator clofibrate. Biochim Biophys Acta 1994; 1201: 203-216.
49 De Craemer D. et al. 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 1994; 35: 1241-1250.
50 Norseth J. The effect of feeding rats with partially hydrogenated marine oil or rapeseed oil on the chain shortening of erucic acid in perfused heart. Biochim Biophys Acta 1979; 575: 1-9.
51 Kvannes J. et al. On the mechanism of stimulation of peroxisomal beta-oxidation in rat heart by partially hydrogenated fish oil. Biochim Biophys Acta 1995; 1255: 39-49.
52 Fahimi HD. et al. Increased myocardial catalase in rats fed ethanol. Am J Pathol 1979; 96: 373-390.
53 Kino M. Chronic effects of ethanol under partial inhibition of catalase activity in the rat heart: light and electron microscopic observations. J Mol Cell Cardiol 1981; 13: 5-21.
54 Karnati S. et al. Mammalian SOD2 is exclusively located in mitochondria and not present in peroxisomes. Histochem Cell Biol 2013; 140: 105-117.
55 Liepinsh E. et al. Activated peroxisomal fatty acid metabolism improves cardiac recovery in ischemia-reperfusion. Naunyn Schmiedebergs Arch Pharmacol 2013; 386: 541-550.
56 Tabibiazar R. et al. Transcriptional profiling of the heart reveals chamber-specific gene expression patterns. Circ Res 2003; 93: 1193-1201.
57 Oberley TD. et al. Immunohistochemical localisation of antioxidant enzymes in adult Syrian hamster tissues and during kidney development. Am J Pathol 1990; 137: 199-214.
58 Grant P. et al. The biogenesis protein PEX14 is an optimal marker for the identification and localisation of peroxisomes in different cell types, tissues, and species in morphological studies. Histochem Cell Biol 2013; 140: 423-442.
59 Huber A. et al. A subtle interplay between three Pex11 proteins shapes de novo formation and fission of peroxisomes. Traffic 2012; 13: 157-167.
60 Koch J. et al. PEX11 family members are membrane elongation factors that coordinate peroxisome proliferation and maintenance. J Cell Sci 2010; 123: 3389-3400.
61 Dreyer C. et al. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell 1992; 68: 879-887.
62 Cheng L. et al. Peroxisome proliferator-activated receptor delta activates fatty acid oxidation in cultured neonatal and adult cardiomyocytes. Biochem Biophys Res Commun 2004; 313: 277-286.
63 Liu J. et al. Peroxisome proliferator-activated receptor beta/delta activation in adult hearts facilitates mitochondrial function and cardiac performance under pressure-overload condition. Hypertension 2011; 57: 223-230.
64 Blasi ER. et al. Effects of chronic PPAR-agonist treatment on cardiac structure and function, blood pressure, and kidney in healthy sprague-dawley rats. PPAR Res 2009; 2009: 237865.
65 Chandra V. et al. Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA. Nature 2008; 456: 350-356.
66 Braissant O. et al. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 1996; 137: 354-366.
67 Grabenbauer M. et al. Detection of peroxisomal proteins and their mRNAs in serial sections of fetal and newborn mouse organs. J Histochem Cytochem 2001; 49: 155-164.
68 Burkart EM. et al. Nuclear receptors PPARbeta/delta and PPARalpha direct distinct metabolic regulatory programs in the mouse heart. J Clin Invest 2007; 117: 3930-3939.
69 Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 1990; 347: 645-650.
70 Tugwood JD. et al. The mouse peroxisome proliferator activated receptor recognizes a response element in the 5’ flanking sequence of the rat acyl CoA oxidase gene. EMBO J 1992; 11: 433-439.
71 Stanley WC. et al. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 2005; 85: 1093-1129.
72 Wu P. et al. Adaptive increase in pyruvate dehydrogenase kinase 4 during starvation is mediated by peroxisome proliferator-activated receptor alpha. Biochem Biophys Res Commun 2001; 287: 391-396.
73 Huang B. et al. Regulation of pyruvate dehydrogenase kinase expression by per-oxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin. Diabetes 2002; 51: 276-283.
74 Kerbey AL. et al. Regulation of pyruvate dehydrogenase in rat heart. Mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: role of coenzyme A, acetylcoenzyme A and reduced and oxidized nicotinamide-ade-nine dinucleotide. Biochem J 1976; 154: 327-348.
75 Wieland O. et al. Active and inactive forms of pyruvate dehydrogenase in rat heart and kidney: effect of diabetes, fasting, and refeeding on pyruvate dehy-drogenase interconversion. Arch Biochem Biophys 1971; 143: 593-601.
76 Watanabe K. et al. Constitutive regulation of cardiac fatty acid metabolism through peroxisome proliferator-activated receptor alpha associated with agedependent cardiac toxicity. J Biol Chem 2000; 275: 22293-22299.
77 Luptak I. et al. Decreased contractile and metabolic reserve in peroxisome proliferator-activated receptor-alpha-null hearts can be rescued by increasing glucose transport and utilisation. Circulation 2005; 112: 2339-2346.
78 Finck BN. et al. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest 2002; 109: 121-130.
79 Finck BN. The PPAR regulatory system in cardiac physiology and disease. Cardiovasc Res 2007; 73: 269-277.
80 Madrazo JA, Kelly DP. The PPAR trio: regulators of myocardial energy metabolism in health and disease. J Mol Cell Cardiol 2008; 44: 968-975.
81 Gilde AJ, Van Bilsen M. Peroxisome proliferator-activated receptors (PPARS): regulators of gene expression in heart and skeletal muscle. Acta Physiol Scand 2003; 178: 425-434.
82 Son NH. et al. Cardiomyocyte expression of PPARgamma leads to cardiac dysfunction in mice. J Clin Invest 2007; 117: 2791-2801.
83 Duan SZ. et al. Cardiomyocyte-specific knockout and agonist of peroxisome proliferator-activated receptor-gamma both induce cardiac hypertrophy in mice. Circ Res 2005; 97: 372-379.
84 Xu Y. et al. PPAR-gamma activation fails to provide myocardial protection in ischemia and reperfusion in pigs. Am J Physiol Heart Circ Physiol 2005; 288: H1314-1323.
85 Yew T, Toh SA, Millar JS. Selective peroxisome proliferator-activated receptor-gamma modulation to reduce cardiovascular risk in patients with insulin resistance. Recent Pat Cardiovasc Drug Discov 2012; 7: 33-41.
86 Shimizu M. et al. Peroxisome proliferator-activated receptor subtypes differentially cooperate with other transcription factors in selective transactivation of the perilipin/PEX11 alpha gene pair. J Biochem 2006; 139: 563-573.
87 Weng H. et al. Pex11alpha deficiency impairs peroxisome elongation and division and contributes to nonalcoholic fatty liver in mice. Am J Physiol Endocrinol Metab 2013; 304: E187-E196.
88 Schrader M. et al. Expression of PEX11beta mediates peroxisome proliferation in the absence of extracellular stimuli. J Biol Chem 1998; 273: 29607-29614.
89 Agrimi G. et al. The human gene SLC25A17 encodes a peroxisomal transporter of coenzyme A, FAD and NAD+. Biochem J 2012; 443: 241-247.
90 Xu HE. et al. Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha. Nature 2002; 415: 813-817.
91 Uppenberg J. et al. Crystal structure of the ligand binding domain of the human nuclear receptor PPARgamma. J Biol Chem 1998; 273: 31108-31112.
92 Xu HE. et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell 1999; 3: 397-403.
93 Vanden Heuvel JP. Diet, fatty acids, and regulation of genes important for heart disease. Curr Atheroscler Rep 2004; 6: 432-440.
94 Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circ Res 2004; 95: 568-578.
95 Kalinowska A. et al. Differential effects of chronic, in vivo, PPAR’s stimulation on the myocardial subcellular redistribution of FAT/CD36 and FABPpm. FEBS Lett 2009; 583: 2527-2534.
96 Song S. et al. Peroxisome proliferator activated receptor alpha (PPARalpha) and PPAR gamma coactivator (PGC-1alpha) induce carnitine palmitoyltransferase IA (CPT-1A) via independent gene elements. Mol Cell Endocrinol 2010; 325: 54-63.
97 Kersten S. et al. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest 1999; 103: 1489-1498.
98 Chamouton J. et al. The Peroxisomal 3-keto-acyl-CoA thiolase B Gene Expression Is under the Dual Control of PPARalpha and HNF4alpha in the Liver. PPAR Res 2010; 2010: 352957.
99 Khoo NK. et al. Differential activation of catalase expression and activity by PPAR agonists: Implications for astrocyte protection in anti-glioma therapy. Redox Biol 2013; 1: 70-79.
100 Bjorkman J. et al. Conditional inactivation of the peroxisome biogenesis Pex13 gene by Cre-loxP excision. Genesis 2002; 32: 179-180

Zusatzmaterial