Metabolism of deoxypyrimidines and deoxypyrimidine antiviral analogs in isolated brain mitochondria

Journal of Neurochemistry

Volumn 122, Issue 1, 2012, Pages 126-137

  McCann, Kathleen A ^a,b   Williams, David W ^b   McKee, Edward E ^a,b,c  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF NOTRE DAME   (United States)

^c Central Michigan University College of Medicine   (United States)

Author keywords

brain mitochondria; mitochondrial toxicity; nucleoside reverse transcriptase inhibitors; thymidine kinase 2

Indexed keywords

ANTIVIRUS AGENT; DEOXYCYTIDINE; DEOXYNUCLEOSIDE TRIPHOSPHATE; DEOXYPYRIMIDINE DERIVATIVE; DEOXYURIDINE; LAMIVUDINE; NUCLEOSIDE TRIPHOSPHATE; PYRIMIDINE DERIVATIVE; STAVUDINE; THYMIDINE; UNCLASSIFIED DRUG; ZIDOVUDINE;

ARTICLE; BRAIN MITOCHONDRION; CONTROLLED STUDY; DRUG METABOLISM; HEART MITOCHONDRION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LIVER MITOCHONDRION; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RAT; SCINTILLATION COUNTING;

ANIMALS; BRAIN; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DEOXYCYTIDINE; DEOXYURIDINE; DOSE-RESPONSE RELATIONSHIP, DRUG; KINETICS; MALE; MITOCHONDRIA; NUCLEOTIDASES; PHOSPHORYLATION; PYRIMIDINE NUCLEOSIDES; RATS; RATS, SPRAGUE-DAWLEY; STAVUDINE; THYMIDINE; TIME FACTORS; TRITIUM; ZIDOVUDINE;

RATTUS;

EID: 84862219795     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/j.1471-4159.2012.07765.x     Document Type: Article

References (57)

1. Anderson D. D., Quintero C. M., and, Stover P. J., (2011) Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. Proc. Natl. Acad. Sci. USA. 108, 15163-15168.
2. Arnaudo E., Dalakas M., Shanske S., Moraes C. T., DiMauro S., and, Schon E. A., (1991) Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy. Lancet 337, 508-510.
3. Barroso J. F., Elholm M., and, Flatmark T., (2003) Tight binding of deoxyribonucleotide triphosphates to human thymidine kinase 2 expressed in Escherichia coli. Purification and partial characterization of its dimeric and tetrameric forms. Biochemistry 42, 15158-15169. (Pubitemid 38031715)
4. Bartesaghi S., Betts-Henderson J., Cain K., Dinsdale D., Zhou X., Karlsson A., Salomoni P., and, Nicotera P., (2010) Loss of thymidine kinase 2 alters neuronal bioenergetics and leads to neurodegeneration. Hum. Mol. Genet. 19, 1669-1677.
5. Blanche S., Tardieu M., Rustin P., et al. (1999) Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues. Lancet 354, 1084-1089. (Pubitemid 29452821)
6. Busidan Y., Shi X., and, Dow-Edwards D. L., (2001) AZT distribution in the fetal and postnatal rat central nervous system. J. Pharm. Sci. 90, 1964-1971. (Pubitemid 33144442)
7. Calamandrei G., Valanzano A., Puopolo M., and, Aloe L., (2002) Developmental exposure to the antiretroviral drug zidovudine increases brain levels of brain-derived neurotrophic factor in mice. Neurosci. Lett. 333, 111-114. (Pubitemid 35284897)
8. Chen Y. L., Lin D. W., and, Chang Z. F., (2008) Identification of a putative human mitochondrial thymidine monophosphate kinase associated with monocytic/macrophage terminal differentiation. Genes Cells 13, 679-689.
9. Divi R. L., Einem T. L., Fletcher S. L., et al. (2010). Progressive mitochondrial compromise in brains and livers of primates exposed in utero to nucleoside reverse transcriptase inhibitors (NRTIs). Toxicol. Sci. 118, 191-201.
10. Dorado B., Area E., Ackman H. O., and, Hirano M., (2011) Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation. Hum. Mol. Genet. 20, 155-164.
11. Eriksson S., Kierdaszuk B., Munch-Petersen B., Oberg B., and, Johansson N. G., (1991) Comparison of the substrate specificities of human thymidine kinase 1 and 2 and deoxycytidine kinase toward antiviral and cytostatic nucleoside analogs. Biochem. Biophys. Res. Commun. 176, 586-592.
12. Mario Fasching K. R.-S., and, Gnaiger E., (2010) Mitochondrial Respiration Medium-MiR06. Mitochondrial Physiology Network 14, 1-4.
13. Ferraro P., Pontarin G., Crocco L., Fabris S., Reichard P., and, Bianchi V., (2005) Mitochondrial deoxynucleotide pools in quiescent fibroblasts: a possible model for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). J. Biol. Chem. 280, 24472-24480. (Pubitemid 40934532)
14. Gotz A., Isohanni P., Pihki H., Paetau A., Herva R., Saarenpaa-Heikkila O., Valanne L., Narjavaara S., and, Suomalainen A., (2008) Thymidine kinase 2 defects can cause multi-tissue mtDNA depletion syndrome. Brain 131, 2841-2850.
15. Hammer S. M., Eron J. J. Jr, Reiss P., et al. (2008) Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 300, 555-570.
16. Hanes J. W., and, Johnson K. A., (2007) A novel mechanism of selectivity against AZT by the human mitochondrial DNA polymerase. Nucleic Acids Res. 35, 6973-6983. (Pubitemid 350201815)
17. Ladner R. D., McNulty D. E., Carr S. A., Roberts G. D., and, Caradonna S. J., (1996) Characterization of distinct nuclear and mitochondrial forms of human deoxyuridine triphosphate nucleotidohydrolase. J. Biol. Chem. 271, 7745-7751. (Pubitemid 26107060)
18. Lavie A., Schlichting I., Vetter I. R., Konrad M., Reinstein J., and, Goody R. S., (1997) The bottleneck in AZT activation. Nat. Med. 3, 922-924. (Pubitemid 27353456)
19. Lee H., Hanes J., Johnson K. A., (2003) Toxicity of nucleoside analogues used to treat AIDS and the selectivity of the mitochondrial DNA polymerase. Biochemistry 42, 14711-14719. (Pubitemid 37553499)
20. Letendre S., Marquie-Beck J., Capparelli E., et al. (2008) Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch. Neurol. 65, 65-70.
21. Lewis W., Gonzalez B., Chomyn A., and, Papoian T., (1992) Zidovudine induces molecular, biochemical, and ultrastructural changes in rat skeletal muscle mitochondria. J. Clin. Invest. 89, 1354-1360.
22. Lewis W., Simpson J. F., and, Meyer R. R., (1994) Cardiac mitochondrial DNA polymerase-gamma is inhibited competitively and noncompetitively by phosphorylated zidovudine. Circ. Res. 74, 344-348. (Pubitemid 24029167)
23. Lewis W., Haase C. P., Raidel S. M., Russ R. B., Sutliff R. L., Hoit B. D., and, Samarel A. M., (2001) Combined antiretroviral therapy causes cardiomyopathy and elevates plasma lactate in transgenic AIDS mice. Lab. Invest. 81, 1527-1536. (Pubitemid 33064278)
24. Lim S. E., and, Copeland W. C., (2001) Differential incorporation and removal of antiviral deoxynucleotides by human DNA polymerase gamma. J. Biol. Chem. 276, 23616-23623.
25. Lopez L. C., Akman H. O., Garcia-Cazorla A., et al. (2009) Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase-deficient mice. Hum. Mol. Genet. 18, 714-722.
26. Lund K. C., Peterson L. L., and, Wallace K. B., (2007) Absence of a universal mechanism of mitochondrial toxicity by nucleoside analogs. Antimicrob. Agents Chemother. 51, 2531-2539. (Pubitemid 47047333)
27. Lynx M. D., and, McKee E. E., (2006) 3'-Azido-3'-deoxythymidine (AZT) is a competitive inhibitor of thymidine phosphorylation in isolated rat heart and liver mitochondria. Biochem. Pharmacol. 72, 239-243. (Pubitemid 43850426)
28. Lynx M. D., Bentley A. T., and, McKee E. E., (2006) 3'-Azido-3'- deoxythymidine (AZT) inhibits thymidine phosphorylation in isolated rat liver mitochondria: a possible mechanism of AZT hepatotoxicity. Biochem. Pharmacol. 71, 1342-1348.
29. Lynx M. D., Kang B. K., and, McKee E. E., (2008) Effect of AZT on thymidine phosphorylation in cultured H9c2, U-937, and Raji cell lines. Biochem. Pharmacol. 75, 1610-1615.
30. Lynx M. D., LaClair D. D., and, McKee E. E., (2009) Effects of zidovudine and stavudine on mitochondrial DNA of differentiating 3T3-F442a cells are not associated with imbalanced deoxynucleotide pools. Antimicrob. Agents Chemother. 53, 1252-1255.
31. McKee E. E., Grier B. L., Thompson G. S., Leung A. C., and, McCourt J. D., (1990a) Coupling of mitochondrial metabolism and protein synthesis in heart mitochondria. Am. J. Physiol. 258, E503-510. (Pubitemid 20116399)
32. McKee E. E., Grier B. L., Thompson G. S., and, McCourt J. D., (1990b) Isolation and incubation conditions to study heart mitochondrial protein synthesis. Am. J. Physiol. 258, E492-502. (Pubitemid 20116398)
33. McKee E. E., Bentley A. T., Hatch M., Gingerich J., and, Susan-Resiga D., (2004) Phosphorylation of thymidine and AZT in heart mitochondria: elucidation of a novel mechanism of AZT cardiotoxicity. Cardiovasc. Toxicol. 4, 155-167. (Pubitemid 39310748)
34. Morris G. Jr, Iams T., Slipchenko K., and, McKee E. E., (2009) Origin of pyrimidine deoxyribonucleotide pools in perfused rat heart: implications for 3'-azido-3'-deoxythymidine-dependent cardiotoxicity. Biochem. J. 422, 513-520.
35. Morris G. W., LaClair D. D., and, McKee E. E., (2010) Pyrimidine deoxynucleoside and nucleoside reverse transcriptase inhibitor metabolism in the perfused heart and isolated mitochondria. Antivir. Ther. 15, 587-597.
36. Munch-Petersen B., (2010) Enzymatic regulation of cytosolic thymidine kinase 1 and mitochondrial thymidine kinase 2: a mini review. Nucleosides, Nucleotides Nucleic Acids 29, 363-369.
37. Munch-Petersen B., Cloos L., Tyrsted G., and, Eriksson S., (1991) Diverging substrate specificity of pure human thymidine kinases 1 and 2 against antiviral dideoxynucleosides. J. Biol. Chem. 266, 9032-9038. (Pubitemid 21906614)
38. Ordys B. B., Launay S., Deighton R. F., McCulloch J., and, Whittle I. R., (2010) The role of mitochondria in glioma pathophysiology. Mol. Neurobiol. 42, 64-75.
39. Pai R. B., Pai S. B., Kukhanova M., Dutschman G. E., Guo X., and, Cheng Y. C., (1998) Telomerase from human leukemia cells: properties and its interaction with deoxynucleoside analogues. Cancer Res. 58, 1909-1913. (Pubitemid 28217466)
40. Radivoyevitch T., Munch-Petersen B., Wang L., and, Eriksson S., (2011) A mathematical model of human thymidine kinase 2 activity. Nucleosides, Nucleotides Nucleic Acids 30, 203-209.
41. Redzic Z. B., Malatiali S. A., Craik J. D., Rakic M. L., and, Isakovic A. J., (2009) Blood-brain barrier efflux transport of pyrimidine nucleosides and nucleobases in the rat. Neurochem. Res. 34, 566-573.
42. Saada A., Shaag A., Mandel H., Nevo Y., Eriksson S., and, Elpeleg O., (2001) Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat. Genet. 29, 342-344. (Pubitemid 33096463)
43. Saada A., Shaag A., and, Elpeleg O., (2003) mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency. Mol. Genet. Metab. 79, 1-5. (Pubitemid 36579435)
44. Simpson M. V., Chin C. D., Keilbaugh S. A., Lin T. S., and, Prusoff W. H., (1989) Studies on the inhibition of mitochondrial DNA replication by 3'-azido-3'-deoxythymidine and other dideoxynucleoside analogs which inhibit HIV-1 replication. Biochem. Pharmacol. 38, 1033-1036. (Pubitemid 19088438)
45. Spector R., and, Boose B., (1983) Development and regional distribution of deoxyuridine 5'-triphosphatase in rabbit brain. J. Neurochem. 41, 1192-1195. (Pubitemid 13017098)
46. Suleiman S. A., and, Spector R., (1982) Metabolism of deoxyuridine in rabbit brain. J. Neurochem. 39, 824-830. (Pubitemid 12034978)
47. Susan-Resiga D., Bentley A. T., Lynx M. D., LaClair D. D., and, McKee E. E., (2007) Zidovudine inhibits thymidine phosphorylation in the isolated perfused rat heart. Antimicrob. Agents Chemother. 51, 1142-1149. (Pubitemid 46586786)
48. Suzuki T., Terasaki M., Takemoto-Hori C., Hanada T., Ueda T., Wada A., and, Watanabe K., (2001) Proteomic analysis of the mammalian mitochondrial ribosome. Identification of protein components in the 28 s small subunit. J. Biol. Chem. 276, 33181-33195.
49. Tozser J., (2001) HIV inhibitors: problems and reality. Ann. N. Y. Acad. Sci. 946, 145-159. (Pubitemid 33127215)
50. Varatharajan L., and, Thomas S. A., (2009) The transport of anti-HIV drugs across blood-CNS interfaces: summary of current knowledge and recommendations for further research. Antiviral Res. 82, A99-109.
51. Wang L., and, Eriksson S., (2000) Cloning and characterization of full-length mouse thymidine kinase 2: the N-terminal sequence directs import of the precursor protein into mitochondria. Biochem. J. 351, 469-476.
52. Wang L., and, Eriksson S., (2010) Tissue specific distribution of pyrimidine deoxynucleoside salvage enzymes shed light on the mechanism of mitochondrial DNA depletion. Nucleosides, Nucleotides Nucleic Acids 29, 400-403.
53. Wang L., Munch-Petersen B., Herrstrom Sjoberg A., Hellman U., Bergman T., Jornval H., and, Eriksson S., (1999) Human thymidine kinase 2: molecular cloning and characterisation of the enzyme activity with antiviral and cytostatic nucleoside substrates. FEBS Lett. 443, 170-174. (Pubitemid 29078626)
54. Wang J., Su C., Neuhard J., and, Eriksson S., (2000) Expression of human mitochondrial thymidine kinase in Escherichia coli: correlation between the enzymatic activity of pyrimidine nucleoside analogues and their inhibitory effect on bacterial growth. Biochem. Pharmacol. 59, 1583-1588. (Pubitemid 30229892)
55. Wang L., Sun R., and, Eriksson S., (2011) The kinetic effects on thymidine kinase 2 by enzyme-bound dTTP may explain the mitochondrial side effects of antiviral thymidine analogs. Antimicrob. Agents Chemother. 55, 2552-2558.
56. Xu Y., Johansson M., and, Karlsson A., (2008) Human UMP-CMP kinase 2, a novel nucleoside monophosphate kinase localized in mitochondria. J. Biol. Chem. 283, 1563-1571.
57. Zhou X., Solaroli N., Bjerke M., Stewart J. B., Rozell B., Johansson M., and, Karlsson A., (2008). Progressive loss of mitochondrial DNA in thymidine kinase 2 deficient mice. Hum. Mol. Genet. 17, 2329-2335.