Mitochondria as cell targets of AZT (zidovudine)

General Pharmacology

Volumn 31, Issue 4, 1998, Pages 531-538

  Barile, Maria ^a   Valenti, Daniela ^a   Quagliariello, Ernesto ^a   Passarella, Salvatore ^b  

^a UNIVERSITY OF BARI   (Italy)

^b Dipto di Sci Animali Vegetali e D   (Italy)

Author keywords

3' Azido 3' deoxythymidine (AZT); Acquired immuno deficiency syndrome; AZT toxicity; Mitochondria

Indexed keywords

ADENINE NUCLEOTIDE TRANSLOCASE; ADENYLATE KINASE; DNA POLYMERASE; MITOCHONDRIAL DNA; ZIDOVUDINE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; CELL ENERGY; DRUG EFFECT; HUMAN; MITOCHONDRIAL RESPIRATION; MITOCHONDRION; NONHUMAN; PRIORITY JOURNAL; RAT; RESPIRATORY CHAIN; REVIEW;

ACQUIRED IMMUNODEFICIENCY SYNDROME; ANIMALS; CELLS, CULTURED; DNA, MITOCHONDRIAL; DNA-DIRECTED DNA POLYMERASE; HUMANS; MITOCHONDRIA; THYMINE NUCLEOTIDES; ZIDOVUDINE;

EID: 0032190598     PISSN: 03063623     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0306-3623(98)00041-X     Document Type: Review

References (56)

1. Agarwal R.P., Olivero O.A. Genotoxicity and mitochondrial damage in human lymphocytic cells chronically exposed to 3′-azido-2′,3′-dideoxythymidine. Mutat. Res. 390:1997;223-231.
2. Aggarwal A., Al-Talib K., Alabrash M. Type B lactic acidosis in an AIDS patient treated with zidovudine. Md. Med. 45:1996;929-931.
3. Arnaudo E., Dalakas M.C., Shanske S., Moraes C.T., DiMauro S., Schon E.A. Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy. Lancet. 337:1991;508-510.
4. Atlante A. and Passarella S. AZT side effect on mitochondria does not depend on either inhibition of electron flow or mitochondrial uncoupling. Int. J. Mol. Med. 1, 601-603.
5. Balzarini J., Herdewijn P., De Clercq E. Differential patterns of intracellular metabolism of 2′,3′-didehydro-2′,3′-dideoxythymidine and 3′-azido-2′,3′-dideoxythymidine, two potent antihuman immunodeficiency virus compounds. J. Biol. Chem. 264:1989;6127-6133.
6. Barile M., Valenti D., Hobbs G.A., Abruzzese M.F., Keibaugh S.A., Passarella S., Quagliariello E., Simpson M.V. Mechanism of toxicity of 3′-azido-3′-deoxythymidine. its interaction with adenylate kinase Biochem. Pharmac. 48:1994;1405-1412.
7. Barile M., Valenti D., Passarella S., Quagliariello E. 3′-Azido-3′-deoxythymidine uptake into isolated rat liver mitochondria and impairment of ADP/ATP translocator. Biochem. Pharmac. 53:1997;913-920.
8. Casademont J., Barrientos A., Grau J.M., Pedrol E., Estivill X., Urbano-Marquez A., Nunes V. The effect of zidovudine on skeletal muscle mtDNA in HIV-1 infected patients with mild or no muscle dysfunction. Brain. 119:1996;1357-1364.
9. Chariot P., Gherardi R. Partial cytochrome c oxidase deficiency and cytoplasmic bodies in patients with zidovudine myopathy. Neuromuscul. Dis. 5:1991;357-363.
10. Chen S.C., Barker S.M., Mitchell D.H., Stevens S.M., O'Neill P., Cunningham A.L. Current zidovudine-induced myopathy and hepatotoxicity in patients treated for human immunodeficiency virus (HIV) infection. Pathology. 24:1992;109-111.
11. Copeland W.C., Chen M.S., Wang T.S.-F. Human DNA polymerase α and β are able to incorporate anti-HIV deoxynucleotides into DNA. J. Biol. Chem. 267:1992;21459-21464.
12. Corcuera T., Pindado M.T., Lopez-Bravo A., Martinez-Rodriguez R., Picazo-Talavera A., Gomez-Aduado F., Ronan-Contreras M., Perez-Alvarez M.J., Garcia A., Alonso-Martin M.J. Histochemical and ultrastructural changes induced by zidovudine in mitochondria of rat cardiac muscle. Eur. J. Histochem. 38:1994;311-318.
13. Corcuera T., Alonso M.J., Picazo A., Gomez F., Roldan M., Abad M., Munoz E., Lopez-Bravo A. Hepatic morphological induced by zidovudine (ZDV) in an experimental model. Pathol. Res. Pract. 192:1996;182-187.
14. Cretton E.M., Xie M.Y., Bevan R.J., Goudgaon N.M., Schinazi R.F., Sommadossi J.P. Catabolism of 3′-azido-3′-deoxythymidine in hepatocytes and liver microsomes, with evidence of formation of 3′-amino-3′-deoxythymidine, a highly toxic catabolite for human bone marrow cells. Mol. Pharmac. 39:1991;258-266.
15. Cupler E.J., Danon M.J., Jay C., Hench K., Ropka M., Dalakas M.C. Early features of zidovudine-associated myopathy. histopathological findings and clinical correlations Acta Neuropathol. 90:1995;1-6.
16. Dalakas M.C., Bethesda M.D., Pezeshkpour G.H. AZT-induced destructive inflammatory myopathy with abnormal mitochondria (DIM-Mi). study of seven patients Neurology. 38(Suppl. 1):1989;152.
17. Dalakas M.C., Illa I., Pezeshkpour G.H., Laukatis J.P., Cohen B., Griffin J.L. Mitochondria myopathy caused by long-term zidovudine therapy. N. Engl. J. Med. 322:1990;1098-1105.
18. Dalakas M.C., Leon-Monzon M.E., Bernardini I., Gahl W.A., Jay C.A. Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage. Ann. Neurol. 35:1994;482-487.
19. Eriksson S., Xu B., Clayton D.A. Efficient incorporation of anti-HIV deoxynucleotides by recombinant yeast mitochondrial DNA polymerase. J. Biol. Chem. 270:1995;18929-18934.
20. Fischl M.A., Richman D.D., Grieco M.H., Gottlieb M.S., Volberding P.A., Laskin O.L., Leedom J.M., Groopman J.E., Mildvan D., Hirsch M.S., Jackson G.G., Durack D.T., Nusinoff L.S. The efficacy of azidothymidine (AZT) in the treatment of the patients with AIDS and AIDS-related complex. a double-blind, placebo-controlled trial N. Engl. J. Med. 317:1987;185-191.
21. Frick L.W., Nelson D.J., St. Clair M.H., Furman P.A., Krenitsky T.A. Effects of 3′-azido-3′-deoxythymidine on the deoxynucleotide triphosphate pools in cultured human cells. Biochem. Biophys. Res. Commun. 154:1988;124-129.
22. Furman P.A., Fyfe J.A., St. Clair M.H., Weinhold K., Rideout J.L., Freeman G.A., Lehrman S.N., Bolognesi D.P., Broder S., Mitsuya H., Barry D.W. Phosphorylation of 3′-azido-3′-deoxythymidine and selective interaction of the 5′-triphosphate with human immunodeficiency virus reverse transcriptase. Proc. Natl. Acad. Sci. USA. 83:1986;8333-8337.
23. Hall E.T., Yan J.-P., Melancon P., Kuchta R.D. 3′-Azido-3′-deoxythymidine potently inhibits protein glycosylation. a novel mechanism for AZT cytotoxicity J. Biol. Chem. 269:1994;14355-14358.
24. Hao Z., Cooney D.A., Hartman N.R., Perno C.F., Fridland A., DeVico A.L., Sarngadharan M.G., Broder S., Johns D. Factors determining the activity of 2′,3′-dideoxynucleosides in suppressing human immunodeficiency virus in vitro. Mol. Pharmac. 34:1988;431-435.
25. Hayakawa M., Ogawa T., Sugiyama S., Tanaka M., Ozawa T. Massive conversion of guanosine to 8-hydroxy-guanosine in mouse liver mitochondria DNA by administration of azidothymidine. Biochem. Biophys. Res. Commun. 176:1991;87-93.
26. Herzberg N.H., Zorn I., Zwart R., Portegies P., Bolhuis P.A. Major growth and minor decrease in mitochondrial enzyme activity in cultured human muscle cells after exposure to zidovudine. Muscle Nerve. 15:1992;706-710.
27. Hobbs G.A., Keilbaugh S.A., Simpson M.V. The Friend murine erythroleukemia cell, a model system for studying the association between bone marrow toxicity induced by 3′-azido-3′-deoxythymidine and dideoxynucleoside inhibition of mtDNA replication. Biochem. Pharmac. 43:1992;1397-1400.
28. Hobbs G.A., Keilbaugh S.A., Rief P.M., Simpson M.V. Cellular targets of 3′-azido-3′-deoxythymidine. an early (non-delayed) effect on oxidative phosphorylation Biochem. Pharmac. 50:1992;381-390.
29. Izuda S., Saneyoshi M., Sakurai T., Suzuki M., Kojima K., Yoshida S. The 5′-triphosphate of 3′-azido-3′-deoxythymidine and 2′,3′-dideoxynucleosides inhibit DNA polymerase γ by different mechanisms. Biochem. Biophys. Res. Commun. 179:1991;776-783.
30. Lamperth L., Dalakas M.C., Dagani F., Anderson J., Ferrari R. Abnormal skeletal and cardiac muscle mitochondria induced by zidovudine (AZT) in human muscle in vitro and in animal model. Lab. Invest. 65:1991;742-751.
31. Lewis L.D., Hamzeh F.M., Lietman P.S. Ultrastructural changes associated with reduced mitochondrial DNA and impaired mitochondrial function in the presence of 2′ 3′-dideoxycytidine. Antimicrob. Agents Chemother. 36:1992;2061-2065.
32. Lewis W., Papoian T., Gonzales B., Louie H., Kelly D.P., Payne R.M., Grody W.W. Mitochondrial ultrastructural and molecular changes induced by zidovudine in rat hearts. Lab. Invest. 65:1991;228-236.
33. Lewis W., Simpson S., Meyer R.R. Cardiac mitochondrial DNA polymerase-γ is inhibited competitively and noncompetitively by phosphorylated zidovudine. Circ. Res. 74:1994;344-348.
34. Linnane A.W., Degli Esposti M., Generowicz M., Luff A.R., Nagley P. The universality of bioenergetic disease and amelioration with redox therapy. Biochim. Biophys. Acta. 1271:1995;191-194.
35. Mhiri C.M.D., Baudrimont P.D.M., Bonne G.M.S., Geny C.M.D., Degoul F.M.S., Marsac M.D., Gherardi R.M.D. Zidovudine myopathy. a distinctive disorder associated with mitochondrial dysfunction Ann. Neurol. 29:1991;604-614.
36. Mitsuya H., Broder S. Strategies for antiviral therapy in AIDS. Nature. 325:1987;773-778.
37. Modica-Napolitano J.S. AZT causes tissue-specific inhibition of mitochondrial bioenergetic function. Biochem. Biophys. Res. Commun. 194:1993;170-177.
38. Morgello S., Wolfe D., Godfrey E., Feinstein R., Tagliati M., Simpson D.M. Mitochondrial abnormalities in human immunodeficiency virus-associated myopathy. Acta Neuropathol. 90:1995;366-374.
39. Olano J.P., Boruck M.J., Wen J.W., Haque A.K. Massive hepatic steatosis and lactic acidosis in a patient with AIDS who received zidovudine. Clin. Infect. Dis. 21:1995;973-976.
40. Ono K., Nakane H., Herdwijn P., Balzarini J., DeClerq E. Differential inhibitory effects of several pyrimidine 2′,3′-dideoxynucleoside 5′-triphosphates on the activities of reverse transcriptase and various cellular DNA polymerases. Mol. Pharmac. 35:1989;578-583.
41. Peters B.S., Winer J., Landon D.N., Stotter A., Pinching A.J. Mitochondrial myopathy with chronic zidovudine therapy in AIDS. Q. J. Med. 86:1993;5-15.
42. Pezeshkpour G., Illa I., Dalakas M.C. Ultrastructural characteristics and DNA immunocytochemistry in human immunodeficiency virus and zidovudine-associated myopathies. Hum. Pathol. 22:1991;1281-1288.
43. Richman D.D., Fischl M.A., Grieco M.H., Gottlieb M.S., Volberding P.A., Laskin O.L., Leedom J.M., Groopman J.E., Mildvan D., Hirsch M.S., Jackson G.G., Durack D.T., Nusinoff L.S. The toxicity of azidothymidine (AZT) in the treatment of the patients with AIDS and AIDS-related complex. a double-blind, placebo-controlled trial N. Engl. J. Med. 317:1987;192-197.
44. Schröder J.M., Kaldenbach T., Piroth W. Nuclear and mitochondrial changes of cocultivated spinal cord, spinal ganglia and muscle fibers following treatment with various doses of zidovudine. Acta Neuropathol. 92:1996;138-149.
45. Semino-Mora M.C., Leon-Monzon M.E., Dalakas M.C. Effect of L-carnitine on the zidovudine-induced destruction of human myotubes I. L-carnitine prevents the myotoxicity of AZT in vitro Lab. Invest. 71:1994;102-112. a.
46. Semino-Mora M.C., Leon-Monzon M.E., Dalakas M.C. The effect of L-carnitine on the AZT-induced destruction of human myotubes II. treatment with L-carnitine improves the AZT-induced changes and prevents further destruction Lab. Invest. 71:1994;773-781. b.
47. Simpson D.M., Citak K.A., Godfrey E., Godbold J., Wolfe D.E. Myopathies associated with human immunodeficiency virus and zidovudine. can their effects be distinguished? Neurology. 43:1993;971-976.
48. Simpson M.V., Chin C.D., Keilbaugh S.A., Lin T.S., Prusoff W.H. Studies on the inhibition of mitochondrial DNA replication by 3′-azido-3′-deoxythymidine. Biochem. Pharmac. 38:1989;1033-1036.
49. Sinnwell T.M., Sivakumar K., Soueidan S., Jay C., Frank J.A., McLaughlin A.C., Dakalas M.C. Metabolic abnormalities in skeletal muscle of patients receiving zidovudine therapy observed by 31P in vivo magnetic resonance spectroscopy. J. Clin. Invest. 96:1995;126-131.
50. Sommadossi J.P., Carlisle R., Zhou Z. Cellular pharmacology of 3′-azido-3′-deoxythymidine with evidence of incorporation into DNA of human bone marrow cells. Mol. Pharmac. 36:1989;9-14.
51. Till M., McDonell K.B. Myopathy with human immunodeficiency virus type 1 (HIV-1) infection. HIV-1 or zidovudine? Ann. Intern. Med. 113:1990;492-494.
52. Tomerelli G., Tonin P., Spadaro M., Tilia G., Orrico D., Barelli A., Bonetti B., Monaco S., Salviati A., Morocutti C. AZT-induced myopathy. Ital. J. Neurol. Sci. 13:1992;723-728.
53. Wang H., Lemire B.D., Cass C.E., Weiner J.H., Michalak M., Penn A.M., Fliegel L. Zidovudine and dideoxynucleosides deplete wild-type mitochondrial DNA levels and increase deleted mitochondrial levels in cultured Kearns-Sayre syndrome fibroblasts. Biochim. Biophys. Acta. 1316:1996;51-59.
54. 31P magnetic resonance spectroscopy suggests impaired mitochondrial function in AZT-treated HIV-infected patients. Neurology. 42:1992;619-623.
55. Yarchoan R., Klecker R.W., Weinhold K.J. Administration of 3′-azido-3′-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet. 1:1986;575-580.
56. Zimmerman T.S., Mahony W.B., Prus K.L. 3′-Azido-3′-deoxythymidine, an unusual nucleoside analogue that permeates the membrane of human erythrocytes and lymphocytes by nonfacilitated diffusion. J. Biol. Chem. 12:1987;5748-5754.