The novel HSP90 inhibitor, PU-H71, suppresses glial cell activation but weakly affects clinical signs of EAE

Journal of Neuroimmunology

Volumn 255, Issue 1-2, 2013, Pages 1-7

  Lisi, Lucia ^a   McGuire, Susan ^b   Sharp, Anthony ^c   Chiosis, Gabriela ^d   Navarra, Pierluigi ^a   Feinstein, Douglas L ^c   Dello Russo, Cinzia ^a  

^a CATHOLIC UNIVERSITY   (Italy)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

^c UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^d MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Astrocytes; EAE; Glial activation; HSP90 inhibitors; Microglia; PU H71

Indexed keywords

GAMMA INTERFERON; HEAT SHOCK PROTEIN 90 INHIBITOR; PU H 71; UNCLASSIFIED DRUG;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; ASTROCYTE; CLINICAL FEATURE; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DRUG EFFECT; FEMALE; GLIA CELL; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; T LYMPHOCYTE ACTIVATION;

ANIMALS; ASTROCYTES; BENZODIOXOLES; CELL LINE, TUMOR; DISEASE MODELS, ANIMAL; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FEMALE; HSP90 HEAT-SHOCK PROTEINS; IMMUNOSUPPRESSIVE AGENTS; MICE; MICE, INBRED C57BL; MICROGLIA; PRIMARY CELL CULTURE; PURINES; RANDOM ALLOCATION; RATS;

EID: 84872672498     PISSN: 01655728     EISSN: 18728421     Source Type: Journal    
DOI: 10.1016/j.jneuroim.2012.10.008     Document Type: Article

References (35)

1. Arroyo D.S., Soria J.A., Gaviglio E.A., Rodriguez-Galan M.C., Iribarren P. Toll-like receptors are key players in neurodegeneration. Int. Immunopharmacol. 2007, 11(10):1415-1421.
2. Barginear M.F., Van Poznak C., Rosen N., Modi S., Hudis C.A., Budman D.R. The heat shock protein 90 chaperone complex: an evolving therapeutic target. Curr. Cancer Drug Targets 2008, 8(6):522-532.
3. Breinig M., Caldas-Lopes E., Goeppert B., Malz M., Rieker R., Bergmann F., Schirmacher P., Mayer M., Chiosis G., Kern M.A. Targeting heat shock protein 90 with non-quinone inhibitors: a novel chemotherapeutic approach in human hepatocellular carcinoma. Hepatology 2009, 50(1):102-112.
4. Caldas-Lopes E., Cerchietti L., Ahn J.H., Clement C.C., Robles A.I., Rodina A., Moulick K., Taldone T., Gozman A., Guo Y., Wu N., de Stanchina E., White J., Gross S.S., Ma Y., Varticovski L., Melnick A., Chiosis G. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc. Natl. Acad. Sci. U. S. A. 2009, 106(20):8368-8373.
5. Cerchietti L.C., Lopes E.C., Yang S.N., Hatzi K., Bunting K.L., Tsikitas L.A., Mallik A., Robles A.I., Walling J., Varticovski L., Shaknovich R., Bhalla K.N., Chiosis G., Melnick A. A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6-dependent B cell lymphomas. Nat. Med. 2009, 15(12):1369-1376.
6. Chiosis G. Discovery and development of purine-scaffold Hsp90 inhibitors. Curr. Top. Med. Chem. 2006, 6(11):1183-1191.
7. Chiosis G., Lucas B., Huezo H., Solit D., Basso A., Rosen N. Development of purine-scaffold small molecule inhibitors of Hsp90. Curr. Cancer Drug Targets 2003, 3(5):371-376.
8. Chiosis G., Vilenchik M., Kim J., Solit D. Hsp90: the vulnerable chaperone. Drug Discov. Today 2004, 9(20):881-888.
9. Constantinescu C.S., Farooqi N., O'Brien K., Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br. J. Pharmacol. 2011, 164(4):1079-1106.
10. Dello Russo C., Polak P.E., Mercado P.R., Spagnolo A., Sharp A., Murphy P., Kamal A., Burrows F.J., Fritz L.C., Feinstein D.L. The heat-shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin suppresses glial inflammatory responses and ameliorates experimental autoimmune encephalomyelitis. J. Neurochem. 2006, 99(5):1351-1362.
11. Dello Russo C., Lisi L., Tringali G., Navarra P. Involvement of mTOR kinase in cytokine dependent microglial activation and cell proliferation. Biochem. Pharmacol. 2009, 78(9):1242-1251.
12. Feinstein D.L., Galea E., Gavrilyuk V., Brosnan C.F., Whitacre C.C., Dumitrescu-Ozimek L., Landreth G.E., Pershadsingh H.A., Weinberg G., Heneka M.T. Peroxisome proliferator-activated receptor-gamma agonists prevent experimental autoimmune encephalomyelitis. Ann. Neurol. 2002, 51(6):694-702.
13. Fletcher J.M., Lalor S.J., Sweeney C.M., Tubridy N., Mills K.H. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin. Exp. Immunol. 2010, 162(1):1-11.
14. Galea E., Reis D.J., Fox E.S., Xu H., Feinstein D.L. CD14 mediate endotoxin induction of nitric oxide synthase in cultured brain glial cells. J. Neuroimmunol. 1996, 64(1):19-28.
15. Gavrilyuk V., Dello Russo C., Heneka M.T., Pelligrino D., Weinberg G., Feinstein D.L. Norepinephrine increases I kappa B alpha expression in astrocytes. J. Biol. Chem. 2002, 277(33):29662-29668.
16. He H., Zatorska D., Kim J., Aguirre J., Llauger L., She Y., Wu N., Immormino R.M., Gewirth D.T., Chiosis G. Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90. J. Med. Chem. 2006, 49(1):381-390.
17. Heneka M.T., Sharp A., Klockgether T., Gavrilyuk V., Feinstein D.L. The heat shock response inhibits NF-kappaB activation, nitric oxide synthase type 2 expression, and macrophage/microglial activation in brain. J. Cereb. Blood Flow Metab. 2000, 20(5):800-811.
18. Heneka M.T., Sharp A., Murphy P., Lyons J.A., Dumitrescu L., Feinstein D.L. The heat shock response reduces myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in mice. J. Neurochem. 2001, 77(2):568-579.
19. Kim Y.S., Alarcon S.V., Lee S., Lee M.J., Giaccone G., Neckers L., Trepel J.B. Update on Hsp90 inhibitors in clinical trial. Curr. Top. Med. Chem. 2009, 9(15):1479-1492.
20. Lisi L., Navarra P., Feinstein D.L., Dello Russo C. The mTOR kinase inhibitor rapamycin decreases iNOS mRNA stability in astrocytes. J. Neuroinflammation 2011, 8:1.
21. Lisi L., Navarra P., Cirocchi R., Sharp A., Stigliano E., Feinstein D.L., Dello Russo C. Rapamycin reduces clinical signs and neuropathic pain in a chronic model of experimental autoimmune encephalomyelitis. J. Neuroimmunol. 2012, 243(1-2):43-51.
22. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 2001, 25(4):402-408.
23. Makhnevych T., Houry W.A. The role of Hsp90 in protein complex assembly. Biochim. Biophys. Acta 2012, 1823(3):674-682.
24. Murphy P., Sharp A., Shin J., Gavrilyuk V., Dello Russo C., Weinberg G., Sharp F.R., Lu A., Heneka M.T., Feinstein D.L. Suppressive effects of ansamycins on inducible nitric oxide synthase expression and the development of experimental autoimmune encephalomyelitis. J. Neurosci. Res. 2002, 67(4):461-470.
25. Osawa Y., Lowe E.R., Everett A.C., Dunbar A.Y., Billecke S.S. Proteolytic degradation of nitric oxide synthase: effect of inhibitors and role of hsp90-based chaperones. J. Pharmacol. Exp. Ther. 2003, 304(2):493-497.
26. Pearl L.H., Prodromou C., Workman P. The Hsp90 molecular chaperone: an open and shut case for treatment. Biochem. J. 2008, 410(3):439-453.
27. Rivest S. Molecular insights on the cerebral innate immune system. Brain Behav. Immun. 2003, 17(1):13-19.
28. Sanchez A.C., Davis R.L., Syapin P.J. Identification of cis-regulatory regions necessary for robust Nos2 promoter activity in glial cells: indirect role for NF-κB. J. Neurochem. 2003, 86(6):1379-1390.
29. Sharp A.J., Polak P.E., Simonini V., Lin S.X., Richardson J.C., Bongarzone E.R., Feinstein D.L. P2x7 deficiency suppresses development of experimental autoimmune encephalomyelitis. J. Neuroinflammation 2008, 5:33.
30. Sosa R.A., Forsthuber T.G. The critical role of antigen-presentation-induced cytokine crosstalk in the central nervous system in multiple sclerosis and experimental autoimmune encephalomyelitis. J. Interferon Cytokine Res. 2011, 31(10):753-768.
31. Vairano M., Dello Russo C., Pozzoli G., Battaglia A., Scambia G., Tringali G., Aloe-Spiriti M.A., Preziosi P., Navarra P. Erythropoietin exerts anti-apoptotic effects on rat microglial cells in vitro. Eur. J. Neurosci. 2002, 16(4):584-592.
32. Whitesell L., Bagatell R., Falsey R. The stress response: implications for the clinical development of hsp90 inhibitors. Curr. Cancer Drug Targets 2003, 3(5):349-358.
33. Yoshida M., Xia Y. Heat shock protein 90 as an endogenous protein enhancer of inducible nitric-oxide synthase. J. Biol. Chem. 2003, 278(38):36953-36958.
34. Zhang H., Burrows F. Targeting multiple signal transduction pathways through inhibition of Hsp90. J. Mol. Med. 2004, 82(8):488-499.
35. Zhao R., Houry W.A. Molecular interaction network of the Hsp90 chaperone system. Adv. Exp. Med. Biol. 2007, 594:27-36.