Targeted delivery of radioprotective agents to mitochondria

Molecular Interventions

Volumn 8, Issue 6, 2008, Pages 294-302

  Zabbarova, Irina ^a   Kanai, Anthony ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (3 AMINOPROPYLAMINO)ETHANETHIOL; ALPHA TOCOPHEROL; AMIFOSTINE; ANTIINFLAMMATORY AGENT; ASCORBIC ACID; CATION; GRAMICIDIN S; IMMUNOMODULATING AGENT; MANGANESE SUPEROXIDE DISMUTASE; MELATONIN; N(G) METHYLARGININE; NITRIC OXIDE SYNTHASE; NITROXIDE; NITROXIDE DERIVATIVE; PEPTIDE; PROTEIN; RADIOPROTECTIVE AGENT; RESVERATROL; RETINOL; SS PEPTIDE; TEMPOL; TROLOX C; UNCLASSIFIED DRUG;

ADENOVIRUS; ANTIOXIDANT ACTIVITY; APOPTOSIS; BLOOD CLOTTING; DIARRHEA; DRUG APPROVAL; DRUG DELIVERY SYSTEM; DRUG MECHANISM; DRUG METABOLISM; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; GENE THERAPY; HEAD AND NECK CANCER; HUMAN; HYPOTENSION; IONIZING RADIATION; IRRADIATION; JAUNDICE; MITOCHONDRION; NAUSEA; NEUROPROTECTION; NONHUMAN; OVARY CANCER; PLASMID; RADIATION INJURY; RADIATION PROTECTION; REVIEW; SIDE EFFECT; VOMITING;

ANIMALS; DRUG DELIVERY SYSTEMS; HUMANS; MITOCHONDRIA; NEOPLASMS; RADIATION-PROTECTIVE AGENTS; RADIATION-SENSITIZING AGENTS;

EID: 58549084994     PISSN: 15340384     EISSN: 15432548     Source Type: Journal    
DOI: 10.1124/mi.8.6.7     Document Type: Review

References (79)

1. Epperly, M.W., Gretton, J.E., Sikora, C.A., et al. Mitochondrial localization of superoxide dismutase is required for decreasing radiation-induced cellular damage. Radiat. Res. 160, 568-578 (2003).
2. Greenberger, J.S., Kagan, V.E., Pearce, L., Boriseniao, G., Tyurina, Y., and Epperly, M.W. Modulation of redox signal transduction pathways in the treatment of cancer. Antioxid. Redox. Signal. 3, 347-359 (2001).
3. Feinendegen, L.E., Pollycove, M., and Neumann, R.D. Whole-body responses to low-level radiation exposure: New concepts in mammalian radiobiology. Exp. Hematol. 35, 37-46 (2007).
4. Kadhim, M.A., Hill, M.A., and Moore, S.R. Genomic instability and the role of radiation quality. Radiat. Prot. Dosimetry 122, 221-217 (2006).
5. Amundson, S.A., Bittner, M., and Fornace, A.J., Jr. Functional genomics as a window on radiation stress signaling. Oncogene 22, 5828-5833 (2003).
6. Valerie, K., Yacoub, A., Hagan, M.P., et al. Radiation-induced cell signaling: Inside-out and outside-in. Mol. Cancer Ther. 6, 789-801 (2007).
7. Kim, D.W., Huamani, J., Fu, A., and Hallahan, D.E. Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 64, 38-46 (2006).
8. Chinnaiyan, P., Allen, G.W., and Harari, P.M. Radiation and new molecular agents, part II: Targeting HDAC, HSP90, IGF-1R, PI3K, and Ras. Semin. Radiat. Oncol. 16, 59-64 (2006).
9. Gulbins, E. and Kolesnick, R. Raft ceramide in molecular medicine. Oncogene 22, 7070-7077 (2003).
10. Limoli, C.L., Kaplan, M.I., Giedzinski, E., and Morgan, W.F. Attenuation of radiation-induced genomic instability by free radical scavengers and cellular proliferation. Free Radic. Biol. Med. 31, 10-19 (2001).
11. Leach, J.K., Van Tuyle, G., Lin, P.S., Schmidt-Ullrich, R., Mikkelsen, R.B. Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. Cancer Res. 61, 3894-3901 (2001).
12. Leach, J.K., Black, S.M., Schmidt-Ullrich, R.K., and Mikkelsen, R.B. Activation of constitutive nitric-oxide synthase activity is an early signaling event induced by ionizing radiation. J. Biol. Chem. 277, 15400-15406 (2002).
13. Brizel, D,M. Pharmacologic approaches to radiation protection. J. Clin. Oncol. 25, 4084-4089 (2007).
14. Moss, R.W. Do antioxidants interfere with radiation therapy for cancer? Integr. Cancer Ther. 6, 281-292 (2007).
15. Praetorius, N.P. and Mandal, T.K. Alternate delivery route for amifostine as a radio-/chemo-protecting agent. J. Pharm. Pharmacol. 60, 809-815 (2008).
16. Culotta, V.C., Yang, M., and O'Halloran, T.V. Activation of superoxide dismutases: Putting the metal to the pedal. Biochim. Biophys. Acta 1763, 747-758 (2006).
17. Greenberger, J.S. and Epperly, M.W. Review. Antioxidant gene therapeutic approaches to normal tissue radioprotection and tumor radiosensitization. In Vivo (2007). 21, 141-146.
18. Kanai, A., Zabbarova, I., Amoscato, A., Epperly, M., Xiao, J.,and Wipf, P. Mitochondrial targeting of radioprotectants using peptidyl conjugates. Org. Biomol. Chem. 5, 307-309 (2007).
19. Soule, B.P., Hyodo, F., Matsumoto, K., et al. Therapeutic and clinical applications of nitroxide compounds. Antioxid. Redox. Signal 9, 1731-1743 (2007).
20. Prasad, K.N., Cole, W.C., Kumar, B., and Che Prasad, K. Pros and cons of antioxidant use during radiation therapy. Cancer Treat Rev. 28, 79-91 (2002).
21. Shirazi, A., Ghobadi, G., and Ghazi-Khansari, M. A radiobiological review on melatonin: A novel radioprotector. J. Radiat. Res. (Tokyo) 48, 263-272 (2007).
22. Kanai, A., Epperly, M., Pearce, L. et al. Differing roles of mitochondrial nitric oxide synthase in cardiomyocytes and urothelial cells. Am. J. Physiol. Heart Circ. Physiol. 286, H13-H21 (2004).
23. Zhao, W., Diz, D.I., and Robbins, M.E. Oxidative damage pathways in relation to normal tissue injury. Br. J. Radiol. 80, S23-S31 (2007).
24. Park, K. and Lee, J.H. Protective effects of resveratrol on UVB-irradiated HaCaT cells through attenuation of the caspase pathway. Oncol. Rep. 19, 413-417 (2008).
25. Hosseinimehr, S.J. Trends in the development of radioprotective agents. Drug Discov. Today 12, 794-805 (2007).
26. Takagi, Y., Choi, I.S., Yamashita, T. et al. Immune activation and radioprotection by propolis. Am. J. Chin. Med. 33, 231-240 (2005).
27. Goel, H.C., Agrawala, P.K., Pathania, V., and Malhotra, N. Immunomodulatory and cytoprotective role of RP-1 in gamma-irradiated mice. Mol. Cell Biochem. 254, 73-81 (2003).
28. Armstrong, J.S. Mitochondrial medicine: Pharmacological targeting of mitochondria in disease. Br. J. Pharmacol. 151, 1154-1165 (2007).
29. von Heijne, G. Mitochondrial targeting sequences may form amphiphilic helices. EMBO J. 5, 1335-1342 (1986).
30. Mokranjac, D. and Neupert, W. Thirty years of protein translocation into mitochondria: Unexpectedly complex and still puzzling. Biochim. Biophys. Acta (2008).
31. Hoye, A.T., Davoren, J.E., Wipf, P., Fink, M.P., and Kagan, V.E. Targeting mitochondria. Acc. Chem. Res. 41, 87-97 (2008).
32. Epperly, M.W., Epstein, C.J., Travis, E.L., and Greenberger, J.S. Decreased pulmonary radiation resistance of manganese superoxide dismutase (MnSOD)-deficient mice is corrected by human manganese superoxide dismutase-Plasmid/Liposome (SOD2-PL) intratracheal gene therapy. Radiat. Res. 154, 365-374 (2000).
33. Epperly, M.W., Bray, J.A., Krager, S. et al. Intratracheal injection of adenovirus containing the human MnSOD transgene protects athymic nude mice from irradiation-induced organizing alveolitis. Int. J. Radiat. Oncol. Biol. Phys. 43, 169-181 (1999).
34. Epperly, M.W., Travis, E.L., Sikora, C., and Greenberger, J.S. Manganese [correction of Magnesium] superoxide dismutase (MnSOD) plasmid/liposome pulmonary radioprotective gene therapy: Modulation of irradiation-induced mRNA for IL-I, TNF-alpha, and TGF-beta correlates with delay of organizing alveolitis/fibrosis. Biol. Blood Marrow Transplant. 5, 204-214 (1999).
35. Stickle, R.L., Epperly, M.W., Klein, E., Bray, J.A., and Greenberger, J.S. Prevention of irradiation-induced esophagitis by plasmid/liposome delivery of the human manganese superoxide dismutase transgene. Radiat. Oncol. Investig. 7, 204-17 (1999).
36. Guo, H., Seixas-Silva, J.A., Jr., Epperly, M.W. et al. Prevention of radiation-induced oral cavity mucositis by plasmid/liposome delivery of the human manganese superoxide dismutase (SOD2) transgene. Radiat. Res. (2003). 159, 361-370.
37. Kanai, A.J., Zeidel, M.L., Lavelle, J.P. et al. Manganese superoxide dismutase gene therapy protects against irradiation-induced cystitis. Am J Physiol Renal Physiol 283, F1304-F1312 (2002).
38. Szeto, H.H. Mitochondria-targeted cytoprotective peptides for ischemia-reperfusion injury. Antioxid. Redox. Signal 10, 601-619 (2008).
39. Szeto, H.H. Mitochondria-targeted peptide antioxidants: Novel neuroprotective agents. AAPS J. 8, E521-E531 (2006).
40. Zhao, K., Zhao, G.M., Wu, D. et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J. Biol. Chem. 279, 34682-34690 (2004).
41. Zhao, K., Luo, G., Giannelli, S., and Szeto, H.H. Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell lines. Biochem. Pharmacol. 70, 1796-1806 (2005).
42. Xiao, J., Weisblum, B., and Wipf, P. Electrostatic versus steric effects in peptidomimicry: synthesis and secondary structure analysis of gramicidin S analogues with (E)-alkene peptide isosteres. J. Am. Chem. Soc. 127, 5742-5743 (2005).
43. Wipf, P., Xiao, J., Jiang, J., Mitochondrial targeting of selective electron scavengers: Synthesis and biological analysis of hemigramicidin-TEMPO conjugates. J. Am. Chem. Soc. 127, 12460-12461 (2005).
44. Wipf, P. and Xiao, J. Convergent approach to (E)-alkene and cyclopropane peptide isosteres. Org. Lett. 7, 103-106 (2005).
45. Jiang, J., Kurnikov, I., Belikova, N.A. et al. Structural requirements for optimized delivery, inhibition of oxidative stress, and antiapoptotic activity of targeted nitroxides. J. Pharmacol. Exp. Ther. (320, 1050-1060 2007).
46. Macias, C.A., Chiao, J.W., Xiao, J. et al. Treatment with a novel hemigramicidin-TEMPO conjugate prolongs survival in a rat model of lethal hemorrhagic shock. Ann. Surg. 245, 305-14 (2007).
47. Murphy, M.P. Selective targeting of bioactive compounds to mitochondria. Trends Biotechnol. 15, 326-330 (1997).
48. Smith, R.A., Porteous, C.M., Coulter, C.V., and Murphy, M.P. Selective targeting of an antioxidant to mitochondria. Eur. J. Biochem. 263, 709-716 (1999).
49. Kelso, G.F., Porteous, C.M., Coulter, C.V. et al. Selective targeting of a redox-active ubiquinone to mitochondria within cells: Antioxidant and antiapoptotic properties. J. Biol. Chem. 276, 4588-4596 (2001).
50. Dhanasekaran, A., Kotamraju, S., Karunakaran, C. et al. Mitochondria superoxide dismutase mimetic inhibits peroxide-induced oxidative damage and apoptosis: Role of mitochondrial superoxide. Free Radic. Biol. Med. 39, 567-583 (2005).
51. Dessolin, J., Schuler, M., Quinart, A., De Giorgi, F., Ghosez, L., and Ichas, F. Selective targeting of synthetic antioxidants to mitochondria: Towards a mitochondrial medicine for neurodegenerative diseases? Eur. J. Pharmacol. 447, 155-161 (2002).
52. Murphy, M.P., Echtay, K.S., Blaikie, F.H. et al. Superoxide activates uncoupling proteins by generating carbon-centered radicals and initiating lipid peroxidation: Studies using a mitochondria-targeted spin trap derived from alpha-phenyl-N-tert-butylnitrone. J. Biol. Chem. 278, 48534-48545 (2003).
53. Mugesh, G., du Mont, W.W., and Sies, H. Chemistry of biologically important synthetic organoselenium compounds. Chem. Rev. 101, 2125-2179 (2001).
54. Filipovska, A., Kelso, G.F., Brown, S.E., Beer, S.M., Smith, R.A., and Murphy, M.P. Synthesis and characterization of a triphenylphosphonium-conjugated peroxidase mimetic. Insights into the interaction of ebselen with mitochondria. J. Biol. Chem. 280, 24113-24126 (2005).
55. Brown, S.E., Ross, M.F., Sanjuan-Pla, A. Manas, A.R., Smith, R.A., and Murphy, M.P. Targeting lipoic acid to mitochondria: Synthesis and characterization of a triphenylphosphonium-conjugated alpha-lipoyl derivative. Free Radic. Biol. Med. 42, 1766-1780 (2007).
56. Murphy, M.P. and Smith, R.A. Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annu. Rev. Pharmacol. Toxicol. 47, 629-656 (2007).
57. Murphy, M.P. Targeting lipophilic cations to mitochondria. Biochim. Biophys. Acta 1777, 1028-1031 (2008).
58. Skulachev, V.P. A biochemical approach to the problem of aging: "Megaproject" on membrane-penetrating ions. The first results and prospects. Biochemistry (Mosc) 72, 1385-1396 (2007).
59. Epperly, M.W., Defilippi, S., Sikora, C., Gretton, J., Kalend, A., and Greenberger, J.S. Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthotopic tumors from irradiation. Gene Ther. 7, 1011-1018 (2000).
60. Guo, H., Epperly, M.W., Bernarding, M. et al. Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) intratracheal gene therapy reduction of irradiation-induced inflammatory cytokines does not protect orthotopic Lewis lung carcinomas. In Vivo 17, 13-21 (2003).
61. Epperly, M.W., Wegner, R., Kanai, A.J. et al. Effects of MnSOD-plasmid liposome gene therapy on antioxidant levels in irradiated murine oral cavity orthotopic tumors. Radiat. Res. 167, 289-297 (2007).
62. Li, S., Yan, T., Yang, J.Q., Oberley, T.D., and Oberley, L.W. The role of cellular glutathione peroxidase redox regulation in the suppression of tumor cell growth by manganese superoxide dismutase. Cancer Res. 60, 3927-3939 (2000).
63. Halliwell, B. Oxidants and human disease: Some new concepts. FASEB J. 1, 358-364 (1987).
64. Chabrier, P.E., Auguet, M., Spinnewyn, B. et al. BN 80933, a dual inhibitor of neuronal nitric oxide synthase and lipid peroxidation: A promising neuroprotective strategy. Proc. Natl. Acad. Sci. USA 96, 10824-10829 (1999).
65. Ding-Zhou, L., Marchand-Verrecchia, C., Palmier, B. et al. Neuroprotective effects of (S)-N-[4-[4-[(3,4-Dihydro-6-hydroxy-2,5,7,8- tetramethyl-2H-1-benzopyran-2-yl)carbonyl]-1-piperazinyl]phenyl] -2-thiophenecarboximid-amide (BN 80933), an inhibitor of neuronal nitric-oxide synthase and an antioxidant, in model of transient focal cerebral ischemia in mice. J Pharmacol. Exp. Ther. 306, 588-594 (2003).
66. Dawson, V.L. Potent neuroprotectants linked to bifunctional inhibition. Proc. Natl. Acad. Sci. USA 96, 10557-10558 (1999).
67. Pou, S., Pou, W.S., Bredt, D.S., Snyder, S.H., and Rosen, G.M. Generation of superoxide by purified brain nitric oxide synthase. J. Biol. Chem. 267, 24173-24176 (1992).
68. Stuehr, D.J. Enzymes of the L-arginine to nitric oxide pathway. J. Nutr. 134, 2748S-2751S; discussion 65S-67S (2004).
69. Spinnewyn, B., Cornet, S., Auguet, M., and Chabrier, P.E. Synergistic protective effects of antioxidant and nitric oxide synthase inhibitor in transient focal ischemia. J. Cereb. Blood Flow. Metab. 19, 139-143 (1999).
70. Bundy, G.L., Banitt, L.S., Dobrowolski, P.J. et al. Synthesis of 2,4-Di-1-pyrrolidinyl-9H-pyrimido[4,5-b]indoles, including antiasthma clinical candidate PNU-142731A. Org. Process Res. Devel. 5, 144-151 (2001).
71. Montebugnoli, D., Bravo, P., Brenna, E. et al. Traceless solid-phase synthesis of 2,4,6-chlorodiamino and triaminopyrimidines. Thetrahedron 59, 7147-7156 (2003).
72. Sleight, A.J., Boess, F.G., Bos, M., Levet-Trafit, B., Riemer, C., and Bourson, A. Characterization of Ro 04-6790 and Ro 63-0563: Potent and selective antagonists at human and rat 5-HT6 receptors. Br. J. Pharmacol. 124, 556-562 (1998).
73. Belka, C., Budach, W., Kortmann, R.D., and Bamberg, M. Radiation induced CNS toxicity - Molecular and cellular mechanisms. Br. J. Cancer 85, 1233-1239 (2001).
74. Vorotnikova, E., Tries, M., and Braunhut, S. Retinoids and TIMP1 prevent radiation-induced apoptosis of capillary endothelial cells. Radiat. Res. 161, 174-184 (2004).
75. Ghafoori, P., Marks, L.B., Vujaskovic, Z., and Kelsey, C.R. Radiation-induced lung injury. Assessment, management, and prevention. Oncology (Williston Park) 22, 37-47; discussion 52-53 (2008).
76. Kruse, J.J., Bomhoff-Wijdenes, I.F., Poele, J.A., and Stewart, F.A. Fractalkine: An important candidate for directing periglomerular leukocyte accumulation in irradiated mouse kidneys. Acta Oncol. 46, 945-950 (2007).
77. Cotrim, A.P., Hyodo, F., Matsumoto, K. et al. Differential radiation protection of salivary glands versus tumor by Tempol with accompanying tissue assessment of Tempol by magnetic resonance imaging. Clin. Cancer Res. 13, 4928-4933 (2007).
78. Nair, C.K., Parida, D.K., and Nomura, T. Radioprotectors in radiotherapy. J. Radiat. Res. (Tokyo) 42, 21-37 (2001).
79. Mathew, D., Nair, C.K., Jacob, J.A. et al. Ascorbic acid monoglucoside as antioxidant and radioprotector. J. Radiat. Res. (Tokyo) 48, 369-76 (2007).