Small Molecule Inhibition of Ligand-Stimulated RAGE-DIAPH1 Signal Transduction

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Manigrasso, Michaele B ^a   Pan, Jinhong ^b   Rai, Vivek ^a,d   Zhang, Jinghua ^a   Reverdatto, Sergey ^b   Quadri, Nosirudeen ^a   DeVita, Robert J ^c   Ramasamy, Ravichandran ^a   Shekhtman, Alexander ^b   Schmidt, Ann Marie ^a  

^a NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

^b STATE UNIVERSITY OF NEW YORK   (United States)

^c RJD Medicinal Chemistry and Drug Discovery Consulting LLC   (United States)

^d INSTITUTE OF LIFE SCIENCES   (India)

Author keywords

[No Author keywords available]

Indexed keywords

ADVANCED GLYCATION END PRODUCT RECEPTOR; AGER PROTEIN, MOUSE; SIGNAL TRANSDUCING ADAPTOR PROTEIN;

ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; GENETICS; HUMAN; METABOLISM; MOUSE; SIGNAL TRANSDUCTION;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADVANCED GLYCOSYLATION END PRODUCT-SPECIFIC RECEPTOR; ANIMALS; HUMANS; MICE; SIGNAL TRANSDUCTION;

EID: 84960105896     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep22450     Document Type: Article

References (71)

1. Daffu, G. et al. Radical roles for RAGE in the pathogenesis of oxidative stress in cardiovascular diseases and beyond. Int. J. Mol. Sci. 14, 19891-19910 (2013).
2. Litwinoff, E. M., Hurtado Del Pozo, C., Ramasamy, R. & Schmidt, A. M. Emerging targets for therapeutic development in diabetes and its complications: The RAGE signaling pathway. Clin. Pharmacol. Ther. (2015).
3. Manigrasso, M. B., Juranek, J., Ramasamy, R. & Schmidt, A. M. Unlocking the biology of RAGE in diabetic microvascular complications. Trends Endocrinol. Metab. 25, 15-22 (2014).
4. Ramasamy, R., Yan, S. F. & Schmidt, A. M. The diverse ligand repertoire of the receptor for advanced glycation endproducts and pathways to the complications of diabetes. Vascul. Pharmacol. 57, 160-167 (2012).
5. Neeper, M. et al. Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J. Biol. Chem. 267, 14998-15004 (1992).
6. Koch, M. et al. Structural basis for ligand recognition and activation of RAGE. Structure 18, 1342-1352 (2010).
7. Park, H., Adsit, F. G. & Boyington, J. C. The 1.5 Å crystal structure of human receptor for advanced glycation endproducts (RAGE) ectodomains reveals unique features determining ligand binding. J. Biol. Chem. 285, 40762-40770 (2010).
8. Xue, J. et al. Advanced glycation end product recognition by the receptor for AGEs. Structure 19, 722-732 (2011).
9. Lander, H. M. et al. Activation of the receptor for advanced glycation end products triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress. J. Biol. Chem. 272, 17810-17814 (1997).
10. McDonald, D. R., Bamberger, M. E., Combs, C. K. & Landreth, G. E. beta-Amyloid fibrils activate parallel mitogen-activated protein kinase pathways in microglia and THP1 monocytes. J. Neurosci. 18, 4451-4460 (1998).
11. Hudson, B. I. et al. Interaction of the RAGE cytoplasmic domain with diaphanous-1 is required for ligand-stimulated cellular migration through activation of Rac1 and Cdc42. J. Biol. Chem. 283, 34457-34468 (2008).
12. Huang, J. S. et al. Role of receptor for advanced glycation end-product (RAGE) and the JAK/STAT-signaling pathway in AGEinduced collagen production in NRK-49F cells. J. Cell. Biochem. 81, 102-113 (2001).
13. Hirose, A., Tanikawa, T., Mori, H., Okada, Y. & Tanaka, Y. Advanced glycation end products increase endothelial permeability through the RAGE/Rho signaling pathway. FEBS Lett. 584, 61-66 (2010).
14. Leclerc, E., Fritz, G., Weibel, M., Heizmann, C. W. & Galichet, A. S100B and S100A6 differentially modulate cell survival by interacting with distinct RAGE (receptor for advanced glycation end products) immunoglobulin domains. J. Biol. Chem. 282, 31317-31331 (2007).
15. Shang, L. et al. RAGE modulates hypoxia/reoxygenation injury in adult murine cardiomyocytes via JNK and GSK-3beta signaling pathways. PLoS One 5, e10092 (2010).
16. Toure, F. et al. Formin mDia1 mediates vascular remodeling via integration of oxidative and signal transduction pathways. Circ. Res. 110, 1279-1293 (2012).
17. Harja, E. et al. Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its ligands in apoE-/- mice. J. Clin. Invest. 118, 183-194 (2008).
18. Kühn, S. & Geyer, M. Formins as effector proteins of Rho GTPases. Small GTPases 5, e29513 (2014).
19. Young, K. G. & Copeland, J. W. Formins in cell signaling. Biochim. Biophys. Acta 1803, 183-190 (2010).
20. Kislinger, T. et al. N(epsilon)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression. J. Biol. Chem. 274, 31740-31749 (1999).
21. Bianchi, R., Kastrisianaki, E., Giambanco, I. & Donato, R. S100B protein stimulates microglia migration via RAGE-dependent upregulation of chemokine expression and release. J. Biol. Chem. 286, 7214-7226 (2011).
22. Medapati, M. R. et al. RAGE Mediates the Pro-Migratory Response of Extracellular S100A4 in Human Thyroid Cancer Cells. Thyroid 25, 514-527 (2015).
23. Chang, J. S. et al. Oxygen deprivation triggers upregulation of early growth response-1 by the receptor for advanced glycation end products. Circ. Res. 102, 905-913 (2008).
24. Rai, V. et al. Signal transduction in Receptor for Advanced Glycation End Products (RAGE): solution structure of C-terminal RAGE and its binding to mDia1. J. Biol. Chem. 287, 5133-5144 (2012).
25. Xie, J. et al. Hexameric calgranulin C (S100A12) binds to the receptor for advanced glycated end products (RAGE) using symmetric hydrophobic target-binding patches. J. Biol. Chem. 282, 4218-4231 (2007).
26. Xue, J. et al. The receptor for advanced glycation end products (RAGE) specifically recognizes methylglyoxal-derived AGEs. Biochemistry 53, 3327-3335 (2014).
27. Deane, R. et al. A multimodal RAGE-specific inhibitor reduces amyloid beta-mediated brain disorder in a mouse model of Alzheimer disease. J. Clin. Invest. 122, 1377-1392 (2012).
28. Sturchler, E., Galichet, A., Weibel, M., Leclerc, E. & Heizmann, C. W. Site-specific blockade of RAGE-Vd prevents amyloid-beta oligomer neurotoxicity. J. Neurosci. 28, 5149-5158 (2008).
29. Sillerud, L. O. & Larson, R. S. Design and structure of peptide and peptidomimetic antagonists of protein-protein interaction. Curr. Protein Pept. Sci. 6, 151-169 (2005).
30. Zhao, L. & Chmielewski, J. Inhibiting protein-protein interactions using designed molecules. Curr. Opin. Struct. Biol. 15, 31-34 (2005).
31. Shuker, S. B., Hajduk, P. J., Meadows, R. P. & Fesik, S. W. Discovering high-affinity ligands for proteins: SAR by NMR. Science 274, 1531-1534 (1996).
32. Blanc, A., Pandey, N. R. & Srivastava, A. K. Synchronous activation of ERK 1/2, p38mapk and PKB/Akt signaling by H2O2 in vascular smooth muscle cells: potential involvement in vascular disease (review). Int. J. Mol. Med. 11, 229-234 (2003).
33. Hofmann, M. A. et al. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97, 889-901 (1999).
34. Liu, M. et al. Simvastatin suppresses vascular inflammation and atherosclerosis in ApoE(-/-) mice by downregulating the HMGB1-RAGE axis. Acta Pharmacol. Sin. 34, 830-836 (2013).
35. Tesch, G. et al. Deletion of bone-marrow-derived receptor for AGEs (RAGE) improves renal function in an experimental mouse model of diabetes. Diabetologia 57, 1977-1985 (2014).
36. Kaji, Y. et al. Inhibition of diabetic leukostasis and blood-retinal barrier breakdown with a soluble form of a receptor for advanced glycation end products. Invest. Ophthalmol. Vis. Sci. 48, 858-865 (2007).
37. Christaki, E., Lazaridis, N. & Opal, S. M. Receptor for advanced glycation end products in bacterial infection: is there a role for immune modulation of receptor for advanced glycation end products in the treatment of sepsis? Curr. Opin. Infect. Dis. 25, 304-311 (2012).
38. Song, F. et al. RAGE regulates the metabolic and inflammatory response to high-fat feeding in mice. Diabetes 63, 1948-1965 (2014).
39. Chen, Y. et al. RAGE ligation affects T cell activation and controls T cell differentiation. J. Immunol. 181, 4272-4278 (2008).
40. Lue, L. F. et al. Involvement of microglial receptor for advanced glycation endproducts (RAGE) in Alzheimer's disease: identification of a cellular activation mechanism. Exp. Neurol. 171, 29-45 (2001).
41. Schmidt, A. M. et al. Receptor for advanced glycation end products (AGEs) has a central role in vessel wall interactions and gene activation in response to circulating AGE proteins. Proc. Natl. Acad. Sci. USA 91, 8807-8811 (1994).
42. Bucciarelli, L. G. et al. Receptor for advanced-glycation end products: key modulator of myocardial ischemic injury. Circulation 113, 1226-1234 (2006).
43. Aleshin, A. et al. RAGE modulates myocardial injury consequent to LAD infarction via impact on JNK and STAT signaling in a murine model. Am. J. Physiol. Heart Circ. Physiol. 294, H1823-1832 (2008).
44. Bucciarelli, L. G. et al. RAGE and modulation of ischemic injury in the diabetic myocardium. Diabetes 57, 1941-1951 (2008).
45. Ramasamy, R., Oates, P. J. & Schaefer, S. Aldose reductase inhibition protects diabetic and nondiabetic rat hearts from ischemic injury. Diabetes 46, 292-300 (1997).
46. Ishihara, K., Tsutsumi, K., Kawane, S., Nakajima, M. & Kasaoka, T. The receptor for advanced glycation end-products (RAGE) directly binds to ERK by a D-domain-like docking site. FEBS Lett. 550, 107-113 (2003).
47. Sakaguchi, M. et al. TIRAP, an adaptor protein for TLR2/4, transduces a signal from RAGE phosphorylated upon ligand binding. PLoS One 6, e23132 (2011).
48. Putranto, E. W. et al. Inhibition of RAGE signaling through the intracellular delivery of inhibitor peptides by PEI cationization. Int. J. Mol. Med. 32, 938-944 (2013).
49. Borsi, V., Cerofolini, L., Fragai, M. & Luchinat, C. NMR characterization of the C-terminal tail of full-length RAGE in a membrane mimicking environment. J. Biomol. NMR 54, 285-290 (2012).
50. Metallo, S. J. Intrinsically disordered proteins are potential drug targets. Curr. Opin. Chem. Biol. 14, 481-488 (2010).
51. Nguyen, L. T. et al. Serum stabilities of short tryptophan- and arginine-rich antimicrobial peptide analogs. PLoS One 5 (2010).
52. Sheng, C., Dong, G., Miao, Z., Zhang, W. & Wang, W. State-of-the-art strategies for targeting protein-protein interactions by smallmolecule inhibitors. Chem. Soc. Rev. (2015).
53. Deane, R. et al. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat. Med. 9, 907-913 (2003).
54. Yan, S. D. et al. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature 382, 685-691 (1996).
55. Bangert, A. et al. Critical role of RAGE and HMGB1 in inflammatory heart disease. Proc. Natl. Acad. Sci. USA 113, E155-164 (2016).
56. Daffu, G. et al. RAGE Suppresses ABCG1-Mediated Macrophage Cholesterol Efflux in Diabetes. Diabetes 64, 4046-4060 (2015).
57. Mulrennan, S. et al. The role of receptor for advanced glycation end products in airway inflammation in CF and CF related diabetes. Sci. Rep. 5, 8931 (2015).
58. Zeng, S. et al. Opposing roles of RAGE and Myd88 signaling in extensive liver resection. FASEB J. 26, 882-893 (2012).
59. Chen, X. et al. RAGE expression in tumor-associated macrophages promotes angiogenesis in glioma. Cancer Res. 74, 7285-7297 (2014).
60. Nasser, M. W. et al. RAGE mediates S100A7-induced breast cancer growth and metastasis by modulating the tumor microenvironment. Cancer Res. 75, 974-985 (2015).
61. https://clinicaltrials.gov/ct2/show/NCT02080364.
62. Schmidt, A. M. Soluble RAGEs-Prospects for treating & tracking metabolic and inflammatory disease. Vascul. Pharmacol. 72, 1-8 (2015).
63. Yamagishi, S. & Matsui, T. Soluble form of a receptor for advanced glycation end products (sRAGE) as a biomarker. Front. Biosci. (Elite Ed) 2, 1184-1195 (2010).
64. Yonchuk, J. G. et al. Circulating soluble receptor for advanced glycation end products (sRAGE) as a biomarker of emphysema and the RAGE axis in the lung. Am. J. Respir. Crit. Care Med. 192, 785-792 (2015).
65. Cavanagh, J., Fairbrother, W. J., Palmer III, A. G., Rance, M. & Skelton, N. J. Protein NMR Spectroscopy: Principles and Practice. (Academic Press, 2007).
66. Keller, R. L. J. The Computer Aided Resonance Assignment Tutorial. (CANTINA Verlag, 2004).
67. Farmer, B. T. 2nd et al. Localizing the NADP + binding site on the MurB enzyme by NMR. Nat. Struct. Biol. 3, 995-997 (1996).
68. Travo, P., Barrett, G. & Burnstock, G. Differences in proliferation of primary cultures of vascular smooth muscle cells taken from male and female rats. Blood Vessels 17, 110-116 (1980).
69. Srinivasan, S. et al. Glucose regulates monocyte adhesion through endothelial production of interleukin-8. Circ. Res. 92, 371-377 (2003).
70. Ramasamy, R., Hwang, Y. C., Whang, J. & Bergmann, S. R. Protection of ischemic hearts by high glucose is mediated, in part, by GLUT-4. Am. J. Physiol. Heart Circ. Physiol. 281, H290-297 (2001).
71. Hwang, Y. C. et al. Central role for aldose reductase pathway in myocardial ischemic injury. FASEB J. 18, 1192-1199 (2004).