Small molecule activation of adaptive gene expression: Tilorone or its analogs are novel potent activators of hypoxia inducible factor-1 that provide prophylaxis against stroke and spinal cord injury

Annals of the New York Academy of Sciences

Volumn 1147, Issue , 2008, Pages 383-394

  Ratan, Rajiv R ^a,h,i,l   Siddiq, Ambreena ^a,h,i   Aminova, Leila ^b,k   Langley, Brett ^a,h,i   McConoughey, Stephen ^a,h   Karpisheva, Ksenia ^a,h   Lee, Hsin Hwa ^a,h   Carmichael, Thomas ^c   Kornblum, Harley ^c   Coppola, Giovanni ^c   Geschwind, Daniel H ^c,i   Hoke, Ahmet ^d,i   Smirnova, Natalya ^a,h,i   Rink, Cameron ^e   Roy, Sashwati ^e   Sen, Chandan ^e   Beattie, Michael S ^j   Hart, Ron P ^f,i   Grumet, Martin ^f,i   Sun, Dongming ^f,i   Freeman, Robert S ^g   Semenza, Gregg L ^d   Gazaryan, Irina ^a,h,i   more..

^a WEILL CORNELL MEDICAL COLLEGE   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e OHIO STATE UNIVERSITY   (United States)

^f RUTGERS UNIVERSITY   (United States)

^g UNIVERSITY OF ROCHESTER   (United States)

^h New York State Center for Research Excellence in Spinal Cord Injury

ⁱ Adelson Program in Neurorehabilitation and Neural Repair

^j UNIVERSITY OF CALIFORNIA   (United States)

^k UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^l Burke Cornell Medical Research Institute   (United States)

more..

Author keywords

Desferrioxamine; Erythropoietin; Homeostasis; Hypoxia; Hypoxia inducible factor; Hypoxia response element; Iron; Prolyl hydroxylase; Tilorone; Vascular endothelial growth factor

Indexed keywords

2 OXOGLUTARIC ACID; 3,6 DIHYDROXY 9H XANTHEN 9 ONE; DEFEROXAMINE; DEFEROXAMINE MESYLATE; ERYTHROPOIETIN; HYPOXIA INDUCIBLE FACTOR 1; IMMUNOMODULATING AGENT; IRON; IRON CHELATING AGENT; OXYGEN; PROCOLLAGEN PROLINE 2 OXOGLUTARATE 4 DIOXYGENASE; R 10874DA; R 11567DA; R 9536DA; TILORONE; TILORONE DERIVATIVE; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; BIOLUMINESCENCE; BLOOD BRAIN BARRIER; CENTRAL NERVOUS SYSTEM; CEREBROVASCULAR ACCIDENT; CONFERENCE PAPER; CONTROLLED STUDY; DRUG STRUCTURE; ENZYME ACTIVATION; ENZYME INHIBITION; GENE ACTIVATION; GENE EXPRESSION; GENE TARGETING; HEMOCHROMATOSIS; HIGH THROUGHPUT SCREENING; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; IN VITRO STUDY; IRON BINDING CAPACITY; IRON CHELATION; MALE; MIDDLE CEREBRAL ARTERY OCCLUSION; MOLECULAR WEIGHT; MOUSE; NERVE REGENERATION; NEUROIMAGING; NEUROPROTECTION; NONHUMAN; PROTEIN PROCESSING; RAT; REAL TIME POLYMERASE CHAIN REACTION; REPORTER GENE; SPINAL CORD INJURY; STROKE; TREATMENT OUTCOME; TREATMENT RESPONSE;

RODENTIA;

EID: 57649233071     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1196/annals.1427.033     Document Type: Conference Paper

References (28)

1. Savitz, S.I. & M. Fisher. 2007. Future of neuroprotection for acute stroke: in the aftermath of the SAINT trials. Ann Neurol. 61 : 396 402.
2. Ratan, R.R. et al. 2004. Translation of ischemic preconditioning to the patient: prolyl hydroxylase inhibition and hypoxia inducible factor-1 as novel targets for stroke therapy. Strok 35 (11 Suppl 1 2687 2689.
3. Semenza, G.L. 2007. Hypoxia-inducible factor 1 (HIF-1) pathway. Sci. STKE. cm8.
4. Ratan, R.R. et al. 2007. Harnessing hypoxic adaptation to prevent, treat, and repair stroke. J. Mol. Med. 85 : 1331 1338.
5. Freeman, R.S. & M.C. Barone. 2005. Targeting hypoxia-inducible factor (HIF) as a therapeutic strategy for CNS disorders. Curr. Drug Targets CNS Neurol. Disord. 4 : 85 92.
6. Semenza, G.L. 2007. Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1. Biochem. J. 405 : 1 9.
7. Stolze, I.P., D.R. Mole & P.J. Ratcliffe. 2006. Regulation of HIF: prolyl hydroxylases. Novartis Found. Symp. 272 : 15 25 discussion 25-36.
8. Siddiq, A., L.R. Aminova & R.R. Ratan. 2007. Hypoxia inducible factor prolyl 4-hydroxylase enzymes: center stage in the battle against hypoxia, metabolic compromise and oxidative stress. Neurochem. Res. 32 : 931 946.
9. Siddiq, A., et al. 2005. Hypoxia-inducible factor prolyl 4-hydroxylase inhibition. A target for neuroprotection in the central nervous system. J. Biol. Chem. 280 : 41732 41743.
10. Freret, T. et al. 2006. Delayed administration of deferoxamine reduces brain damage and promotes functional recovery after transient focal cerebral ischemia in the rat. Eur. J. Neurosci. 23 : 1757 1765.
11. Woo, K.J. et al. 2006. Desferrioxamine, an iron chelator, enhances HIF- 1alpha accumulation via cyclooxygenase-2 signaling pathway. Biochem. Biophys. Res. Commun. 343 : 8 14.
12. Krueger, R.E. & G.D. Mayer. 1970. Tilorone hydrochloride: an orally active antiviral agent. Science 169 : 1213 1214.
13. Murphy, T.H., R.L. Schnaar & J.T. Coyle. 1990. Immature cortical neurons are uniquely sensitive to glutamate toxicity by inhibition of cystine uptake. FASEB J. 4 : 1624 1633.
14. Bederson, J.B. et al. 1986. Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. Stroke 17 : 1304 1308.
15. Belayev, L. et al. 1996. Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke 27 : 1616 1622 discussion 1623.
16. Swanson, R.A. et al. 1990. A semiautomated method for measuring brain infarct volume. J. Cereb. Blood Flow Metab. 10 : 290 293.
17. Ayoub, I.A. et al. 1999. Nicotinamide reduces infarction up to two hours after the onset of permanent focal cerebral ischemia in Wistar rats. Neurosci. Lett. 259 : 21 24.
18. Hashimoto, M. et al. 2007. Osteopontin-deficient mice exhibit less inflammation, greater tissue damage, and impaired locomotor recovery from spinal cord injury compared with wild-type controls. J. Neurosci. 27 : 3603 3611.
19. Constantini, S. & W. Young. 1994. The effects of methylprednisolone and the ganglioside GM1 on acute spinal cord injury in rats. J. Neurosurg. 80 : 97 111.
20. Semenza, G.L. et al. 1996. Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J. Biol. Chem. 271 : 32529 32537.
21. Heemskerk, J., A.J. Tobin & L.J. Bain. 2002. Teaching old drugs new tricks. Meeting of the Neurodegeneration Drug Screening Consortium, 7-8 April 2002, Washington, DC, USA. Trends Neurosci. 25 : 494 496.
22. Chandra, P. & G.J. Wright. 1977. Tilorone hydrochloride: the drug profile. Top Curr. Chem. 72 : 125 148.
23. Pollard, R.B. 1980. Usages of interferon and interferon inducers in man. Med. Biol. 58 : 57 62.
24. Alcaro, S., F. Ortuso & R.S. Coleman. 2005. Molecular modeling of DNA cross-linking analogues based on the azinomycin scaffold. J. Chem. Inf. Model. 45 : 602 609.
25. Ghosh, P. & S. Kornfeld. 2004. The GGA proteins: key players in protein sorting at the trans-Golgi network. Eur. J. Cell Biol. 83 : 257 262.
26. Treins, C. et al. 2002. Insulin stimulates hypoxia-inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathway. J. Biol. Chem. 277 : 27975 27981.
27. Nishi, K. et al. 2008. LPS induces hypoxia-inducible factor 1 activation in macrophage-differentiated cells in a reactive oxygen species-dependent manner. Antioxid. Redox Signal. 10 : 983 996.
28. Briggs, C.A. et al. 2008. alpha7 nicotinic acetylcholine receptor agonist properties of tilorone and related tricyclic analogues. Br. J. Pharmacol. 153 : 1054 1061.