Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis

Science Translational Medicine

Volumn 5, Issue 175, 2013, Pages

  Ferriero, Rosa ^a   Manco, Giuseppe ^b   Lamantea, Eleonora ^c   Nusco, Edoardo ^a   Ferrante, Maria I ^d   Sordino, Paolo ^d   Stacpoole, Peter W ^e   Lee, Brendan ^f   Zeviani, Massimo ^c   Brunetti Pierri, Nicola ^a,g  

^a TELETHON INSTITUTE OF GENETICS AND MEDICINE TIGEM   (Italy)

^b INSTITUTE OF PROTEIN BIOCHEMISTRY   (Italy)

^c DEPARTMENT OF NEUROSURGERY   (Italy)

^d STAZIONE ZOOLOGICA ANTON DOHRN   (Italy)

^e UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^f BAYLOR COLLEGE OF MEDICINE   (United States)

^g UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ARYLBUTYRIC ACID DERIVATIVE; PYRUVATE DEHYDROGENASE COMPLEX; PYRUVATE DEHYDROGENASE KINASE; RECOMBINANT ENZYME; SERINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN LEVEL; C57BL 6 MOUSE; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG APPROVAL; DRUG INDICATION; ENZYME ACTIVITY; ENZYME BINDING; ENZYME INACTIVATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; ENZYME SUBUNIT; FEMALE; FIBROBLAST; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LACTIC ACIDOSIS; LIVER LEVEL; MALE; MOUSE; MUSCLE LEVEL; NONHUMAN; PARTIAL HEPATECTOMY; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PYRUVATE DEHYDROGENASE COMPLEX DEFICIENCY; WILD TYPE; ZEBRA FISH;

ACIDOSIS, LACTIC; ANIMALS; BRAIN; LIVER; MICE; MUSCLE, SKELETAL; PHENYLBUTYRATES; PHOSPHORYLATION; PYRUVATE DEHYDROGENASE COMPLEX DEFICIENCY DISEASE;

EID: 84875126013     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3004986     Document Type: Article

References (66)

1. M. S. Patel, T. E. Roche, Molecular biology and biochemistry of pyruvate dehydrogenase complexes. FASEB J. 4, 3224-3233 (1990). (Pubitemid 120012568)
2. B. H. Robinson, Lactic acidemia and mitochondrial disease. Mol. Genet. Metab. 89, 3-13 (2006). (Pubitemid 44205482)
3. K. P. Patel, T. W. O'Brien, S. H. Subramony, J. Shuster, P. W. Stacpoole, The spectrum of pyruvate dehydrogenase complex deficiency: Clinical, biochemical and genetic features in 371 patients. Mol. Genet. Metab. 105, 34-43 (2012).
4. B. H. Robinson, K. Chun, N. Mackay, G. Otulakowski, R. Petrova-Benedict, H. Willard, Isolated and combined deficiencies of the a-keto acid dehydrogenase complexes. Ann. N. Y. Acad. Sci. 573, 337-346 (1989). (Pubitemid 20175667)
5. S. D. Cederbaum, J. P. Blass, N. Minkoff, W. J. Brown, M. E. Cotton, S. H. Harris, Sensitivity to carbohydrate in a patient with familial intermittent lactic acidosis and pyruvate dehydrogenase deficiency. Pediatr. Res. 10, 713-720 (1976).
6. R. E. Falk, S. D. Cederbaum, J. P. Blass, G. E. Gibson, R. A. Kark, R. E. Carrel, Ketonic diet in the management of pyruvate dehydrogenase deficiency. Pediatrics 58, 713-721 (1976).
7. I. D.Wexler, S. G. Hemalatha, J.McConnell, N. R. Buist, H. H. Dahl, S. A. Berry, S. D. Cederbaum, M. S. Patel, D. S. Kerr, Outcome of pyruvate dehydrogenase deficiency treated with ketogenic diets. Studies in patients with identical mutations. Neurology 49, 1655-1661 (1997). (Pubitemid 28015134)
8. M. M. Bowker-Kinley, W. I. Davis, P. Wu, R. A. Harris, K. M. Popov, Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. Biochem. J. 329 (Pt. 1), 191-196 (1998). (Pubitemid 28022308)
9. Y. Koga, N. Povalko, K. Katayama, N. Kakimoto, T. Matsuishi, E. Naito, M. Tanaka, Beneficial effect of pyruvate therapy on Leigh syndrome due to a novel mutation in PDH E1a gene. Brain Dev. 34, 87-91 (2012).
10. M. Tanaka, Y. Nishigaki, N. Fuku, T. Ibi, K. Sahashi, Y. Koga, Therapeutic potential of pyruvate therapy for mitochondrial diseases. Mitochondrion 7, 399-401 (2007). (Pubitemid 350082357)
11. H. Komaki, Y. Nishigaki, N. Fuku, H. Hosoya, K. Murayama, A. Ohtake, Y. Goto, H. Wakamoto, Y. Koga, M. Tanaka, Pyruvate therapy for Leigh syndrome due to cytochrome c oxidase deficiency. Biochim. Biophys. Acta 1800, 313-315 (2010).
12. P. W. Stacpoole, L. R. Gilbert, R. E. Neiberger, P. R. Carney, E. Valenstein, D. W. Theriaque, J. J. Shuster, Evaluation of long-term treatment of children with congenital lactic acidosis with dichloroacetate. Pediatrics 121, e1223-e1228 (2008).
13. P. W. Stacpoole, D. S. Kerr, C. Barnes, S. T. Bunch, P. R. Carney, E. M. Fennell, N. M. Felitsyn, R. L. Gilmore, M. Greer, G. N. Henderson, A. D. Hutson, R. E. Neiberger, R. G. O'Brien, L. A. Perkins, R. G. Quisling, A. L. Shroads, J. J. Shuster, J. H. Silverstein, D. W. Theriaque, E. Valenstein, Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children. Pediatrics 117, 1519-1531 (2006). (Pubitemid 46071378)
14. P. Kaufmann, K. Engelstad, Y. Wei, S. Jhung, M. C. Sano, D. C. Shungu, W. S. Millar, X. Hong, C. L. Gooch, X. Mao, J. M. Pascual, M. Hirano, P. W. Stacpoole, S. DiMauro, D. C. De Vivo, Dichloroacetate causes toxic neuropathy in MELAS: A randomized, controlled clinical trial. Neurology 66, 324-330 (2006). (Pubitemid 43739931)
15. T. C. Linn, F. H. Pettit, L. J. Reed, a-Keto acid dehydrogenase complexes. X. Regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation. Proc. Natl. Acad. Sci. U.S.A. 62, 234-241 (1969).
16. L. G. Korotchkina, M. S. Patel, Mutagenesis studies of the phosphorylation sites of recombinant human pyruvate dehydrogenase. Site-specific regulation. J. Biol. Chem. 270, 14297-14304 (1995).
17. L. G. Korotchkina, M. S. Patel, Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase. J. Biol. Chem. 276, 37223-37229 (2001).
18. W. M. Teague, F. H. Pettit, T. L. Wu, S. R. Silberman, L. J. Reed, Purification and properties of pyruvate dehydrogenase phosphatase from bovine heart and kidney. Biochemistry 21, 5585-5592 (1982).
19. B. Huang, R. Gudi, P. Wu, R. A. Harris, J. Hamilton, K. M. Popov, Isoenzymes of pyruvate dehydrogenase phosphatase. DNA-derived amino acid sequences, expression, and regulation. J. Biol. Chem. 273, 17680-17688 (1998). (Pubitemid 28355107)
20. N. Brunetti-Pierri, B. Lanpher, A. Erez, E. A. Ananieva, M. Islam, J. C. Marini, Q. Sun, C. Yu, M. Hegde, J. Li, R. M. Wynn, D. T. Chuang, S. Hutson, B. Lee, Phenylbutyrate therapy for maple syrup urine disease. Hum. Mol. Genet. 20, 631-640 (2011).
21. T. E. Roche, Y. Hiromasa, Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer. Cell. Mol. Life Sci. 64, 830-849 (2007). (Pubitemid 46597752)
22. J. E. Bolden, M. J. Peart, R. W. Johnstone, Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov. 5, 769-784 (2006). (Pubitemid 44348499)
23. A. Pinheiro, I. Faustino, M. J. Silva, J. Silva, R. Sá, M. Sousa, A. Barros, I. T. de Almeida, I. Rivera, Human testis-specific PDHA2 gene: Methylation status of a CpG island in the open reading frame correlates with transcriptional activity. Mol. Genet. Metab. 99, 425-430 (2010).
24. J. Gilbert, S. D. Baker, M. K. Bowling, L. Grochow, W. D. Figg, Y. Zabelina, R. C. Donehower, M. A. Carducci, A phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies. Clin. Cancer Res. 7, 2292-2300 (2001). (Pubitemid 32751627)
25. X. Yu, M. M. Thompson, D. Shi, M. Tuchman, Quantification of benzoic, phenylacetic, and phenylbutyric acids from filter-paper blood spots by gas chromatography-mass spectrometry with stable isotope dilution. Clin. Chem. 47, 351-354 (2001). (Pubitemid 32142941)
26. M. T. Johnson, H. S. Yang, T. Magnuson, M. S. Patel, Targeted disruption of the murine dihydrolipoamide dehydrogenase gene (Dld) results in perigastrulation lethality. Proc. Natl. Acad. Sci. U.S.A. 94, 14512-14517 (1997). (Pubitemid 28041405)
27. M. T. Johnson, S. Mahmood, S. L. Hyatt, H. S. Yang, P. D. Soloway, R. W. Hanson, M. S. Patel, Inactivation of the murine pyruvate dehydrogenase (Pdha1) gene and its effect on early embryonic development. Mol. Genet. Metab. 74, 293-302 (2001). (Pubitemid 33111909)
28. S. E. Brockerhoff, J. B. Hurley, U. Janssen-Bienhold, S. C. Neuhauss, W. Driever, J. E. Dowling, A behavioral screen for isolating zebrafish mutants with visual system defects. Proc. Natl. Acad. Sci. U.S.A. 92, 10545-10549 (1995).
29. S. E. Brockerhoff, J. E. Dowling, J. B. Hurley, Zebrafish retinal mutants. Vision Res. 38, 1335-1339 (1998). (Pubitemid 28239256)
30. M. R. Taylor, H. A. Van Epps, M. J. Kennedy, J. C. Saari, J. B. Hurley, S. E. Brockerhoff, Biochemical analysis of phototransduction and visual cycle in zebrafish larvae. Methods Enzymol. 316, 536-557 (2000). (Pubitemid 30235692)
31. M. R. Taylor, J. B. Hurley, H. A. Van Epps, S. E. Brockerhoff, A zebrafish model for pyruvate dehydrogenase deficiency: Rescue of neurological dysfunction and embryonic lethality using a ketogenic diet. Proc. Natl. Acad. Sci. U.S.A. 101, 4584-4589 (2004). (Pubitemid 38437454)
32. S. C. Neuhauss, O. Biehlmaier, M. W. Seeliger, T. Das, K. Kohler, W. A. Harris, H. Baier, Genetic disorders of vision revealed by a behavioral screen of 400 essential loci in zebrafish. J. Neurosci. 19, 8603-8615 (1999). (Pubitemid 30226778)
33. R. Chioléro, L. Tappy, M. Gillet, J. P. Revelly, H. Roth, C. Cayeux, P. Schneiter, X. Leverve, Effect of major hepatectomy on glucose and lactate metabolism. Ann. Surg. 229, 505-513 (1999). (Pubitemid 30191748)
34. S. E. Buchalter, M. R. Crain, R. Kreisberg, Regulation of lactate metabolism in vivo. Diabetes Metab. Rev. 5, 379-391 (1989). (Pubitemid 19137088)
35. R. A. Kreisberg, Lactate homeostasis and lactic acidosis. Ann. Intern. Med. 92, 227-237 (1980). (Pubitemid 10141585)
36. R. Park, A. I. Arieff, Treatment of lactic acidosis with dichloroacetate in dogs. J. Clin. Invest. 70, 853-862 (1982). (Pubitemid 12038102)
37. M. Tuchman, B. Lee, U. Lichter-Konecki, M. L. Summar, M. Yudkoff, S. D. Cederbaum, D. S. Kerr, G. A. Diaz, M. R. Seashore, H. S. Lee, R. J. McCarter, J. P. Krischer, M. L. Batshaw; Urea Cycle Disorders Consortium of the Rare Diseases Clinical Research Network, Cross-sectional multicenter study of patients with urea cycle disorders in the United States. Mol. Genet. Metab. 94, 397-402 (2008).
38. T. Hitosugi, J. Fan, T. W. Chung, K. Lythgoe, X. Wang, J. Xie, Q. Ge, T. L. Gu, R. D. Polakiewicz, J. L. Roesel, G. Z. Chen, T. J. Boggon, S. Lonial, H. Fu, F. R. Khuri, S. Kang, J. Chen, Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 is important for cancer metabolism. Mol. Cell 44, 864-877 (2011).
39. M. Machius, J. L. Chuang, R. M. Wynn, D. R. Tomchick, D. T. Chuang, Structure of rat BCKD kinase: Nucleotide-induced domain communication in a mitochondrial protein kinase. Proc. Natl. Acad. Sci. U.S.A. 98, 11218-11223 (2001). (Pubitemid 32928709)
40. J. R. Davie, R. M. Wynn, M. Meng, Y. S. Huang, G. Aalund, D. T. Chuang, K. S. Lau, Expression and characterization of branched-chain a-ketoacid dehydrogenase kinase from the rat. Is it a histidine-protein kinase? J. Biol. Chem. 270, 19861-19867 (1995).
41. R. M. Wynn, J. L. Chuang, C. D. Cote, D. T. Chuang, Tetrameric assembly and conservation in the ATP-binding domain of rat branched-chain a-ketoacid dehydrogenase kinase. J. Biol. Chem. 275, 30512-30519 (2000).
42. K. Ono, G. A. Radke, T. E. Roche, M. Rahmatullah, Partial activation of the pyruvate dehydrogenase kinase by the lipoyl domain region of E2 and interchange of the kinase between lipoyl domain regions. J. Biol. Chem. 268, 26135-26143 (1993). (Pubitemid 23361678)
43. E. M. Ciszak, L. G. Korotchkina, P. M. Dominiak, S. Sidhu, M. S. Patel, Structural basis for flipflop action of thiamin pyrophosphate-dependent enzymes revealed by human pyruvate dehydrogenase. J. Biol. Chem. 278, 21240-21246 (2003). (Pubitemid 36806439)
44. M. Kato, R. M. Wynn, J. L. Chuang, S. C. Tso, M. Machius, J. Li, D. T. Chuang, Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: Role of disordered phosphorylation loops. Structure 16, 1849-1859 (2008).
45. E. Ogasawara, K. Nakada, J. Hayashi, Lactic acidemia in the pathogenesis of mice carrying mitochondrial DNA with a deletion. Hum. Mol. Genet. 19, 3179-3189 (2010).
46. K. R. Wagner, M. Kleinholz, G. M. de Courten-Myers, R. E. Myers, Hyperglycemic versus normoglycemic stroke: Topography of brain metabolites, intracellular pH, and infarct size. J. Cereb. Blood Flow Metab. 12, 213-222 (1992).
47. J. Folbergrová, Q. Zhao, K. Katsura, B. K. Siesjö, N-tert-butyl-a-phenylnitrone improves recovery of brain energy state in rats following transient focal ischemia. Proc. Natl. Acad. Sci. U.S.A. 92, 5057-5061 (1995).
48. M. Nedergaard, R. P. Kraig, J. Tanabe, W. A. Pulsinelli, Dynamics of interstitial and intracellular pH in evolving brain infarct. Am. J. Physiol. 260, R581-R588 (1991).
49. H. Widmer, H. Abiko, A. I. Faden, T. L. James, P. R. Weinstein, Effects of hyperglycemia on the time course of changes in energy metabolism and pH during global cerebral ischemia and reperfusion in rats: Correlation of 1H and 31P NMR spectroscopy with fatty acid and excitatory amino acid levels. J. Cereb. Blood Flow Metab. 12, 456-468 (1992).
50. R. P. Kraig, C. K. Petito, F. Plum, W. A. Pulsinelli, Hydrogen ions kill brain at concentrations reached in ischemia. J. Cereb. Blood Flow Metab. 7, 379-386 (1987).
51. B. K. Siesjö, K. Katsura, T. Kristián, Acidosis-related damage. Adv. Neurol. 71, 209-233 (1996).
52. P. A. Li, M. Shamloo, K. Katsura, M. L. Smith, B. K. Siesjö, Critical values for plasma glucose in aggravating ischaemic brain damage: Correlation to extracellular pH. Neurobiol. Dis. 2, 97-108 (1995).
53. R. E. Anderson, W. K. Tan, H. S. Martin, F. B. Meyer, Effects of glucose and PaO2 modulation on cortical intracellular acidosis, NADH redox state, and infarction in the ischemic penumbra. Stroke 30, 160-170 (1999). (Pubitemid 29029458)
54. M. W. Parsons, P. A. Barber, P. M. Desmond, T. A. Baird, D. G. Darby, G. Byrnes, B. M. Tress, S. M. Davis, Acute hyperglycemia adversely affects stroke outcome: A magnetic resonance imaging and spectroscopy study. Ann. Neurol. 52, 20-28 (2002). (Pubitemid 34693739)
55. J. C. Preiser, D. Moulart, J. L. Vincent, Dichloroacetate administration in the treatment of endotoxin shock. Circ. Shock 30, 221-228 (1990). (Pubitemid 20116723)
56. P. Ayala, J. Montenegro, R. Vivar, A. Letelier, P. A. Urroz, M. Copaja, D. Pivet, C. Humeres, R. Troncoso, J. M. Vicencio, S. Lavandero, G. Díaz-Araya, Attenuation of endoplasmic reticulum stress using the chemical chaperone 4-phenylbutyric acid prevents cardiac fibrosis induced by isoproterenol. Exp. Mol. Pathol. 92, 97-104 (2012).
57. K. Srinivasan, S. S. Sharma, Sodium phenylbutyrate ameliorates focal cerebral ischemic/ reperfusion injury associated with comorbid type 2 diabetes by reducing endoplasmic reticulum stress and DNA fragmentation. Behav. Brain Res. 225, 110-116 (2011).
58. X. Qi, T. Hosoi, Y. Okuma, M. Kaneko, Y. Nomura, Sodium 4-phenylbutyrate protects against cerebral ischemic injury. Mol. Pharmacol. 66, 899-908 (2004). (Pubitemid 39319462)
59. C. Mitchell, H. Willenbring, A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice. Nat. Protoc. 3, 1167-1170 (2008).
60. D. C. DeVivo, M. W. Haymond, K. A. Obert, J. S. Nelson, A. S. Pagliara, Defective activation of the pyruvate dehydrogenase complex in subacute necrotizing encephalomyelopathy (Leigh disease). Ann. Neurol. 6, 483-494 (1979). (Pubitemid 10174406)
61. J. C. Baker, X. Yan, T. Peng, S. Kasten, T. E. Roche, Marked differences between two isoforms of human pyruvate dehydrogenase kinase. J. Biol. Chem. 275, 15773-15781 (2000). (Pubitemid 30366876)
62. M. Rahmatullah, T. E. Roche, Modification of bovine kidney pyruvate dehydrogenase kinase activity by CoA esters and their mechanism of action. J. Biol. Chem. 260, 10146-10152 (1985). (Pubitemid 16244107)
63. S. Ravindran, G. A. Radke, J. R. Guest, T. E. Roche, Lipoyl domain-based mechanism for the integrated feedback control of the pyruvate dehydrogenase complex by enhancement of pyruvate dehydrogenase kinase activity. J. Biol. Chem. 271, 653-662 (1996). (Pubitemid 26034911)
64. M. Westerfield, The Zebrafish Book. A Guide for the Laboratory Use of Zebrafish (Danio rerio) (University of Oregon Press, Eugene, ed. 5, 2007).
65. E. Van Otterloo,W. Li, G. Bonde, K. M. Day, M. Y. Hsu, R. A. Cornell, Differentiation of zebrafish melanophores depends on transcription factors AP2 alpha and AP2 epsilon. PLoS Genet. 6, e1001122 (2010).
66. Z. Han, L. Zhong, A. Srivastava, P. W. Stacpoole, Pyruvate dehydrogenase complex deficiency caused by ubiquitination and proteasome-mediated degradation of the E1b subunit. J. Biol. Chem. 283, 237-243 (2008).