DNA Methylation Inhibitor Zebularine Confers Stroke Protection in Ischemic Rats

Translational Stroke Research

Volumn 6, Issue 4, 2015, Pages 296-300

  Dock, Hua ^a   Theodorsson, Annette ^a   Theodorsson, Elvar ^a  

^a LINKÖPING UNIVERSITY   (Sweden)

Author keywords

DNA methylation inhibitor; Ischemic stroke; Neuroprotection; Zebularine

Indexed keywords

NEUROPROTECTIVE AGENT; ZEBULARINE; CYTIDINE; ENZYME INHIBITOR; PYRIMIDIN-2-ONE BETA-RIBOFURANOSIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN INFARCTION SIZE; BRAIN ISCHEMIA; CONTROLLED STUDY; DRUG EFFECT; MALE; MIDDLE CEREBRAL ARTERY OCCLUSION; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; RAT; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; ANALOGS AND DERIVATIVES; ANALYSIS OF VARIANCE; ANIMAL; BRAIN INFARCTION; COMPLICATION; DISEASE MODEL; DOSE RESPONSE; INFARCTION, MIDDLE CEREBRAL ARTERY; REPERFUSION; WISTAR RAT;

ANALYSIS OF VARIANCE; ANIMALS; BRAIN INFARCTION; CYTIDINE; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; INFARCTION, MIDDLE CEREBRAL ARTERY; MALE; RATS; RATS, WISTAR; REPERFUSION;

EID: 84933675360     PISSN: 18684483     EISSN: 1868601X     Source Type: Journal    
DOI: 10.1007/s12975-015-0397-7     Document Type: Article

References (29)

1. Liu R, Yang SH. Window of opportunity: estrogen as a treatment for ischemic stroke. Brain Res. 2013;1514:83–90.
2. Writing Group Members, Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, et al. Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009;119(3):e21–181.
3. WHO Stroke, Cerebrovascular accident. World Health Organization. 2011.Available: http://www.who.int/topics/cerebrovascular accident/en/.
4. Wainer D. Strokes killing younger people as unhealthy habits rise. 2013. Available: http://www.bloomberg.com/news/2013-10-23/strokes-killing-younger-people-as-unhealthy-habits-rise.html.
5. Endre M, Meisel A, Biniszkiewicz D, Namura S, Prass K, Ruscher K, et al. DNA methyltransferase contributes to delayed ischemic brain injury. J Neurosci. 2000;20(9):3175–81.
6. Brown SE, Weaver IG, Meaney MJ, Szyf M. Regional-specific global cytosine methylation and DNA methyltransferase expression in the adult rat hippocampus. Neurosci Lett. 2008;440(1):49–53.
7. Bouchard J, Momparler RL. Incorporation of 5-Aza-2 deoxycytidine-5-triphosphate into DNA. Interactions with mammalian DNApolymerase α and DNA methylase. Mol Pharmacol. 1983;24(1):109–14.
8. Santi DV, Garrett CE, Barr PJ. On the mechanism of inhibition of DNA-cytosine methyltransferases by cytosine analogs. Cell. 1983;33(1):9–10.
9. Kogure K, Kato H. Altered gene expression in cerebral ischemia. Stroke. 1993;24(10):2121–7.
10. Lubbert M. DNA methylation inhibitors in the treatment of leukemias, myelodysplastic syndromes and hemoglobinopathies: clinical results and possible mechanisms of action. Curr Top Microbiol Immunol. 2000;249:135–64.
11. Kim CH, Marquez VE, Mao DT, Haines DR, McCormack JJ. Synthesis of pyrimidin-2-one nucleosides as acid-stable inhibitors of cytidine deaminase. J Med Chem. 1986;29(8):1374–80.
12. Laliberte J, Marquez VE, Momparler RL. Potent inhibitors for the deamination of cytosine arabinoside and 5-aza-2-deoxycytidine by human cytidine deaminase. Cancer Chemother Pharmacol. 1992;30(1):7–11.
13. Gonzalgo ML, Hayashida T, Bender CM, Pao MM, Tsai YC, Gonzales FA, et al. The role of DNA methylation in expression of the p19/p16 locusin human bladder cancer cell lines. Cancer Res. 1998;58(6):1245–52.
14. Driscoll JS, Marquez VE, Plowman J, Liu PS, Kelley JA, Barchi Jr JJ. Antitumor properties of 2(1H)-pyrimidinone riboside (zebularine) and its fluorinated analogues. J Med Chem. 1991;34(11):3280–4.
15. Beisler JA. Isolation, characterization, and properties of a liable hydrolysis product of the antitumor nucleoside, 5-azacytidine. J Med Chem. 1978;21(2):204–8.
16. Holm L, Theodorsson E, Hökfelt T, Theodorsson A. Effects of intracerebroventricular galanin or a galanin receptor 2/3 agonist on the lesion induced by transient occlusion of the middle cerebral artery in female rats. Neuropeptides. 2011;45(1):17–23.
17. Lyko F, Brown B. DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J Natl Cancer Inst. 2005;97(20):1498–506.
18. Ström JO, Ingberg E, Theodorsson E, Theodorsson A. Effects of high and low 17ß-estradiol doses on focal cerebral ischemia: negative results. Sci Rep. 2013;3:3111. doi:10.1038/srep03111.
19. Champion C, Guianvarch D, Senamaud-Beaufort C, Jurkowska RZ, Jeltsch A, Ponger L, et al. Mechanistic insights on the inhibition of c5 DNA methyltransferases by zebularine. PLoS One. 2010;5(8):e12388.
20. Yoshida M, Horinouchi S, Beppu T. Trichostatin A and trapoxin: novel chemical probes for the role of histone acetylation in chromatin structure and function. Bioassays. 1995;17(5):423–30.
21. Eden S, Hashimshony T, Keshet I, Cedar H, Thorne AW. DNA methylation models histone acetylation. Nature. 1998;394(6696):842.
22. Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet. 1998;19(2):187–91.
23. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BT, Eisenmann RN, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 1998;393(6683):386–9.
24. Smallwood A, Esteve PO, Pradhan S, Carey M. Functional cooperation between HP1 and DNMT1 mediates gene silencing. Genes Dev. 2007;21(10):1169–78.
25. Faraco G, Pancani T, Formentini L, Mascaqni P, Fossati G, Leoni F, et al. Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic acid specifically alters gene expression and reduces ischemic injury in the mouse brain. Mol Pharmacol. 2006;70(6):1876–84.
26. Saha RN, Pahan K. HATs and HDACs in neurodegeneration: a tale of disconcerted acetylation homeostasis. Cell Death Differ. 2006;13(4):539–50.
27. Lanzillotta A, Pignataro G, Branca C, Cuomo O, Sarnico I, Benarese M, et al. Targeted acetylation of NF-kappaB/RelA and histones by epigenetic drugs reduces post-ischemic brain injury in mice with an extended therapeutic window. Neurobiol Dis. 2013;49:177–89.
28. Wozniak RJ, Klimecki WT, Lau SS, Feinstein Y, Futscher BW. 5-Aza-2-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene. 2007;26(1):77–90.
29. Krupinski J, Slevin M. Emerging molecular targets for brain repair after stroke. Stroke Res Treat. 2013;2013:473416.