Prolyl 4 Hydroxylase: A Critical Target in the Pathophysiology of Diseases

다국어 초록 (Multilingual Abstract)

Prolyl 4 hydroxylases (P4H) are iron- and 2-oxoglutamate-dependent dioxygenase enzymes and hypoxia-inducible transcription factor (HIF)-P4Hs play a critical role in the regulating oxygen homeostasis in the local tissues as well in the systemic circulation. Over a period of time, a number of prolyl hydroxylase inhibitors and activators have been developed. By employing the pharmacological tools and transgenic knock out animals, the critical role of these enzymes has been established in the pathophysiology of number of diseases including myocardial infarction, congestive heart failure,stroke, neurodegeneration, inflammatory disease, respiratory diseases, retinopathy and others. The present review discusses the different aspects of these enzymes including their pathophysiological role in disease development.

참고문헌 (Reference)

1 Xie G, "expression of prolyl hydroxylase 2 is associated with tumor grade and poor prognosis in patients with colorectal cancer" 237 : 860-866, 2012

2 Evans CE, "Upregulation of hypoxia-inducible factor 1 alpha in local vein wall is associated with enhanced venous thrombus resolution" 128 : 346-351, 2011

3 Wojtaszek P, "Ultrastructural localisation and further biochemical characterisation of prolyl 4- hydroxylase from Phaseolus vulgaris: comparative analysis" 31 : 463-477, 1999

4 Semenza GL, "Transcriptional regulation of genes encoding glycolytic enzymes by hypoxiainducible factor 1" 269 : 23757-23763, 1994

5 Günzler V, "Time-dependent inactivation of chick-embryo prolyl 4-hydroxylase by coumalic acid. Evidence for a syncatalytic mechanism" 242 : 163-169, 1987

6 Ivan M, "The von Hippel-Lindau tumor suppressor protein" 11 : 27-34, 2001

7 Annunen P, "The novel type II prolyl 4-hydroxylase is the main enzyme form in chondrocytes and capillary endothelial cells, whereas the type I enzyme predominates in most cells" 273 : 5989-5992, 1998

8 Tian H, "The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development" 12 : 3320-3324, 1998

9 Chen YR, "The expression of hypoxia- inducible factor-1alpha and its hydroxylases in pulmonary arteries of patient with chronic obstructive pulmonary disease" 28 : 234-238, 2012

10 Myllyharju J, "The exoskeleton collagens in Caenorhabditis elegans are modified by prolyl 4-hydroxylases with unique combinations of subunits" 277 : 29187-29196, 2002

11 Hewitson KS, "The HIF pathway as a therapeutic target" 9 : 704-711, 2004

12 Majamaa K, "The 2-oxoglutarate binding site of prolyl 4-hydroxylase. Identification of distinct subsites and evidence for 2-oxoglutarate decarboxylation in a ligand reaction at the enzyme-bound ferrousion" 138 : 239-245, 1984

13 Jaakkola P, "Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation" 292 : 468-472, 2001

14 Semenza GL, "Targeting HIF-1 for cancer therapy" 3 : 721-732, 2003

15 Günzler V, "Syncatalytic inactivation of prolyl 4-hydroxylase by synthetic peptides containing the unphysiologic amino acid 5- oxaproline" 263 : 19498-19504, 1988

16 Günzler V, "Syncatalytic inactivation of prolyl 4- hydroxylase by anthracyclines" 251 : 365-372, 1988

17 Min JH, "Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling" 296 : 1886-1889, 2002

18 Hon WC, "Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL" 417 : 975-978, 2002

19 Xu Y, "Streptococcal Scl1 and Scl2 proteins form collagen-like triple helices" 277 : 27312-27318, 2002

20 McCaffrey TA, "Specific inhibition of eIF-5A and collagen hydroxylation by a single agent. Antiproliferative and fibrosuppressive effects on smooth muscle cells from human coronary arteries" 95 : 446-455, 1995

21 Minamishima YA, "Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure" 111 : 3236-3244, 2008

22 Brahimi-Horn C, "Signalling via the hypoxia-inducible factor-1alpha requires multiple posttranslational modifications" 17 : 1-9, 2005

23 Kant R, "Remote renal preconditioning-induced cardioprotection: a key role of hypoxia inducible factor-prolyl 4-hydroxylases" 312 : 25-31, 2008

24 Krishnamachary B, "Regulation of colon carcinoma cell invasion by hypoxiainducible factor 1" 63 : 1138-1143, 2003

25 Feldser D, "Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2" 59 : 3915-3918, 1999

26 Bordoli MR, "Prolyl-4-hydroxylase PHD2- and hypoxia-inducible factor 2-dependent regulation of amphiregulin contributes to breast tumorigenesis" 30 : 548-560, 2011

27 Duan LJ, "Prolyl hydroxylase domain protein 2 (PHD2) mediates oxygen-induced retinopathy in neonatal mice" 178 : 1881-1890, 2011

28 Muz B, "Prolyl hydroxylase domain enzyme 2 is the major player in regulating hypoxic responses in rheumatoid arthritis" 64 : 2856-2867, 2012

29 Walmsley SR, "Prolyl hydroxylase 3(PHD3)is essential for hypoxic regulation of neutrophilic inflammation in humans and mice" 121 : 1053-1063, 2011

30 Kivirikko KI, "Prolyl 4-hydroxylases and their protein disulfide isomerase subunit" 16 : 357-368, 1998

31 Friedman L, "Prolyl 4-hydroxylase is required for viability and morphogenesis in Caenorhabditis elegans" 97 : 4736-4741, 2000

32 Kaska DD, "Prolyl 4-hydroxylase from Volvox carteri. A low-Mr enzyme antigenically related to the alpha subunit of the vertebrate enzyme" 256 : 257-263, 1988

33 Kapitsinou PP, "Preischemic targeting of HIF prolyl hydroxylation inhibits fibrosis associated with acute kidney injury" 302 : F1172-F1179, 2012

34 Bernhardt WM, "Preconditional activation of hypoxia-inducible factors ameliorates ischemic acute renal failure" 17 : 1970-1978, 2006

35 Majamaa K, "Partial identity of the 2-oxoglutarate and ascorbate binding sites of prolyl 4-hydroxylase" 261 : 7819-7823, 1986

36 Oehme F, "Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors" 296 : 2002

37 Takizawa S, "Novel neuroprotective agents: a HIF activator and an Akt activator" 52 : 911-912, 2012

38 Knowles HJ, "Novel mechanism of action for hydralazine: induction of hypoxia-inducible factor- 1alpha, vascular endothelial growth factor, and angiogenesis by inhibition of prolyl hydroxylases" 95 : 162-169, 2004

39 Cunliffe CJ, "Novel inhibitors of prolyl 4-hydroxylase. 3. Inhibition by the substrate analogue N-oxaloglycine and its derivatives" 35 : 2652-2658, 1992

40 Giusti S, "Neuroprotection by hypoxic preconditioning involves upregulation of hypoxia-inducible factor- 1 in a prenatal model of acute hypoxia" 90 : 468-478, 2012

41 Francis GS, "Neurohumoral activation in preclinical heart failure. Remodeling and the potential for intervention" 87 (87): IV90-IV96, 1993

42 Ema M, "Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300" 18 : 1905-1904, 1999

43 Helaakoski T, "Molecular cloning of the alpha-subunit of human prolyl 4-hydroxylase: the complete cDNA-derived amino acid sequence and evidence for alternative splicing of RNA transcripts" 86 : 4392-4396, 1989

44 Jaffe R, "Maternal circulation in the first-trimester human placenta--myth or reality?" 176 : 695-705, 1997

45 Lieb ME, "Mammalian EGLN genes have distinct patterns of mRNA expression and regulation" 80 : 421-426, 2002

46 Schneider M, "Loss or silencing of the PHD1 prolyl hydroxylase protects livers of mice against ischemia/ reperfusion injury" 138 : 1143-1154, 2010

47 Tambuwala MM, "Loss of prolyl hydroxylase-1 protects against colitis through reduced epithelial cell apoptosis and increased barrier function" 139 : 2093-2101, 2010

48 Makino Y, "Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression" 414 : 550-554, 2001

49 Lee DW, "Inhibition of prolyl hydroxylase protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- induced neurotoxicity: model for the potential involvement of the hypoxia-inducible factor pathway in Parkinson disease" 284 : 29065-29076, 2009

50 Fielitz J, "Inhibition of prolyl 4-hydroxylase prevents left ventricular remodelling in rats with thoracic aortic banding" 9 : 336-342, 2007

51 Baader E, "Inhibition of prolyl 4-hydroxylase by oxalyl amino acid derivatives in vitro, in isolated microsomes and in embryonic chicken tissues" 300 : 525-530, 1994

52 Fraisl P, "Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease" 8 : 139-152, 2009

53 Nwogu JI, "Inhibition of collagen synthesis with prolyl 4-hydroxylase inhibitor improves left ventricular function and alters the pattern of left ventricular dilatation after myocardial infarction" 104 : 2216-2221, 2001

54 Yun Z, "Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stra13: a mechanism for regulation of adipogenesis by hypoxia" 2 : 331-341, 2002

55 Masson N, "Independent function of two destruction domains in hypoxiainducible factor-alpha chains activated by prolyl hydroxylation" 20 : 5197-5206, 2001

56 Reyes H, "Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor" 256 : 1193-1195, 1992

57 Takahashi Y, "Hypoxic induction of prolyl 4-hydroxylase alpha (I) in cultured cells" 275 : 14139-14146, 2000

58 Ke Q, "Hypoxia-inducible factor-1(HIF-1)" 70 : 1469-1480, 2006

59 Caniggia I, "Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFbeta(3)" 105 : 577-587, 2000

60 Siddiq A, "Hypoxia-inducible factor prolyl 4-hydroxylase inhibition. A target for neuroprotection in the central nervous system" 280 : 41732-41743, 2005

61 Huang LE, "Hypoxia-inducible factor and its biomedical relevance" 278 : 19575-19578, 2003

62 Semenza GL, "Hypoxia-inducible factor 1: master regulator of O2 homeostasis" 8 : 588-594, 1998

63 Wang GL, "Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension" 92 : 5510-5514, 1995

64 Ran R, "Hypoxia preconditioning in the brain" 27 : 87-92, 2005

65 Schipani E, "Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival" 15 : 2865-2876, 2001

66 Kivirikko, KI, "Hydroxylation of proline and lysine residues in collagens and other animal and plant proteins, In Post-Translational Modifications of Proteins" CRC Press 1-51, 1992

67 Hyvärinen J, "Hearts of hypoxia-inducible factor prolyl 4-hydroxylase-2 hypomorphic mice show protection against acute ischemia-reperfusion injury" 285 : 13646-13657, 2010

68 Ryan HE, "HIF-1 alpha is required for solid tumor formation and embryonic vascularization" 17 : 3005-3015, 1998

69 Ockaili R, "HIF-1 activation attenuates postischemic myocardial injury: role for heme oxygenase-1 in modulating microvascular chemokine generation" 289 : H542-H548, 2005

70 Nangaku M, "HIF regulation in kidney disease" 2012

71 Berra E, "HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia" 22 : 4082-4090, 2003

72 Klotzsche-von Ameln A, "HIF prolyl hydroxylase-2 inhibition diminishes tumor growth through matrix metalloproteinase-induced TGFβ activation" 13 : 216-223, 2012

73 Niatsetskaya Z, "HIF prolyl hydroxylase inhibitors prevent neuronal death induced by mitochondrial toxins: therapeutic implications for Huntington's disease and Alzheimer's disease" 12 : 435-443, 2010

74 Johansen JL, "HIF prolyl hydroxylase inhibition increases cell viability and potentiates dopamine release in dopaminergic cells" 115 : 209-219, 2010

75 Masson N, "HIF prolyl and asparaginyl hydroxylases in the biological response to intracellular O(2) levels" 116 : 3041-3049, 2003

76 Ruas JL, "Functional analysis of hypoxia- inducible factor-1 alpha-mediated transactivation. Identification of amino acid residues critical for transcriptional activation and/or interaction with CREB-binding protein" 277 : 38723-38730, 2002

77 Eriksson M, "Evidence for 4-hydroxyproline in viral proteins. Characterization of a viral prolyl 4-hydroxylase and its peptide substrates" 274 : 22131-22134, 1999

78 Asikainen TM, "Enhancement of angiogenic effectors through hypoxiainducible factor in preterm primate lung in vivo" 291 : L588-L595, 2006

79 Tian H, "Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells" 11 : 72-82, 1997

80 Heindryckx F, "Effect of prolyl hydroxylase domain-2 haplodeficiency on the hepatocarcinogenesis in mice" 57 : 61-68, 2012

81 Zhang J, "Effect of conjugated linoleic acid on inhibition of prolyl hydroxylase 1 in hearts of mice" 11 : 22-, 2012

82 Cioffi CL, "Differential regulation of HIF-1 alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells" 303 : 947-953, 2003

83 Kotch LE, "Defective vascularization of HIF-1alpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell death" 209 : 254-267, 1999

84 Tomita S, "Defective brain development in mice lacking the Hif-1alpha gene in neural cells" 23 : 6739-6749, 2003

85 Johnstone IL, "Cuticle collagen genes. Expression in Caenorhabditis elegans" 16 : 21-27, 2000

86 Crews ST, "Control of cell lineage-specific development and transcription by bHLH-PAS proteins" 12 : 607-620, 1998

87 Myllyharju J, "Collagens and collagen-related diseases" 33 : 7-21, 2001

88 Kivirikko KI, "Collagen hydroxylases and the protein disulfide isomerase subunit of prolyl 4-hydroxylases" 72 : 325-398, 1998

89 Helaakoski T, "Cloning, baculovirus expression, and characterization of a second mouse prolyl 4-hydroxylase alpha-subunit isoform: formation of an α2β2 tetramer with the protein disulfide-isomerase/β subunit" 92 : 4427-4431, 1995

90 Annunen P, "Cloning of the human prolyl 4-hydroxylase alpha subunit isoform alpha(II) and characterization of the type II enzyme tetramer. The alpha(I) and alpha(II) subunits do not form a mixed alpha(I)alpha(II)beta2 tetramer" 272 : 17342-17348, 1997

91 Annunen P, "Cloning of the alpha subunit of prolyl 4-hydroxylase from Drosophila and expression and characterization of the corresponding enzyme tetramer with some unique properties" 274 : 6790-6796, 1999

92 Hieta R, "Cloning and characterization of a low molecular weight prolyl 4-hydroxylase from Arabidopsis thaliana. Effective hydroxylation of proline-rich, collagen-like, and hypoxia-inducible transcription factor alpha-like peptides" 277 : 23965-23971, 2002

93 Bao W, "Chronic inhibition of hypoxiainducible factor prolyl 4-hydroxylase improves ventricular performance, remodeling, and vascularity after myocardial infarction in the rat" 56 : 147-155, 2010

94 Srinivas V, "Characterization of an oxygen/redox-dependent degradation domain of hypoxia-inducible factor alpha (HIF-alpha) proteins" 260 : 557-561, 1999

95 Merriweather A, "Characterization and expression of enzymatically active recombinant filarial prolyl 4-hydroxylase" 116 : 185-197, 2001

96 Semenza GL, "Cell-type-specific and hypoxia-inducible expression of the human erythropoietin gene in transgenic mice" 88 : 8725-8729, 1991

97 Hölscher M, "Cardiomyocyte-specific prolyl-4-hydroxylase domain 2 knock out protects from acute myocardial ischemic injury" 286 : 11185-11194, 2011

98 Epstein AC, "C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation" 107 : 43-54, 2001

99 Lushnikova I, "Brief anoxia preconditioning and HIF prolyl-hydroxylase inhibition enhances neuronal resistance in organotypic hippocampal slices on model of ischemic damage" 1386 : 175-183, 2011

100 Ivan M, "Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor" 99 : 13459-13464, 2002

101 Smith MC, "Bacteriophage collagen" 279 : 1834-, 1998

102 Lando D, "Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch" 295 : 858-861, 2002

103 Schlemminger I, "Analogues of dealanylalahopcin are inhibitors of human HIF prolyl hydroxylases" 13 : 1451-1454, 2003

104 Son ED, "Alpha-ketoglutarate stimulates procollagen production in cultured human dermal fibroblasts, and decreases UVB-induced wrinkle formation following topical application on the dorsal skin of hairless mice" PHARMACEUTICAL SOC JAPAN 30 (30): 1395-1399, 2007

105 Forsythe JA, "Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1" 16 : 4604-4613, 1996

106 Wright G, "Activation of the prolyl hydroxylase oxygen-sensor results in induction of GLUT1, heme oxygenase-1, and nitric-oxide synthase proteins and confers protection from metabolic inhibition to cardiomyocytes" 278 : 20235-20239, 2003

107 Warnecke C, "Activation of the hypoxia-inducible factorpathway and stimulation of angiogenesis by application of prolyl hydroxylase inhibitors" 17 : 1186-1188, 2003

108 Elks PM, "Activation of hypoxia-inducible factor-1α (Hif-1α) delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model" 118 : 712-722, 2011

109 Pugh CW, "Activation of hypoxia-inducible factor-1; definition of regulatory domains within the alpha subunit" 272 : 11205-11214, 1997

110 Kamura T, "Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex" 97 : 10430-10435, 2000

111 Hanauske-Abel HM, "A stereochemical concept for the catalytic mechanism of prolylhydroxylase: applicability to classification and design of inhibitors" 94 : 421-455, 1982

112 Chinta SJ, "A possible novel anti-inflammatory mechanism for the pharmacological prolyl hydroxylase inhibitor 3,4-dihydroxybenzoate: implications for use as a therapeutic for Parkinson's disease" 2012 : 364684-, 2012

113 Melillo G, "A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter" 182 : 1683-1693, 1995

114 Winter AD, "A hypodermally expressed prolyl 4-hydroxylase from the filarial nematode Brugia malayi is soluble and active in the absence of protein disulfide isomerase" 278 : 2554-2562, 2003

115 Bruick RK, "A conserved family of prolyl-4-hydroxylases that modify HIF" 294 : 1337-1340, 2001

116 Bruick RK, "A conserved family of prolyl 4- hydroxylases that modify HIF" 294 : 1337-1340, 2001