Advertisement

A multicellular signal transduction network of AGE/RAGE signaling

  • Sowmya Soman
  • Rajesh Raju
  • Varot K. Sandhya
  • Jayshree Advani
  • Aafaque Ahmad Khan
  • H. C. Harsha
  • T. S. Keshava Prasad
  • P. R. Sudhakaran
  • Akhilesh Pandey
  • Puneeth K. Adishesha
Nuts and Bolts

Introduction

Advanced glycation end products (AGEs) are heterogeneous glycated products of proteins, lipids and nucleotides. The major receptor for AGEs, known as receptor for advanced glycation end products (RAGE or AGER), is a multi-ligand transmembrane receptor of immunoglobulin superfamily. It has an extracellular region, a transmembrane domain and a short cytoplasmic domain. Extracellular region of RAGE consists of one V type (critical for ligand binding) and two C type immunoglobulin domains (Schmidt et al. 1994a, b). Although the short cytoplasmic tail of 43 amino acid residues is found to be important for the signaling events mediated by RAGE, it does not have any known domain or motif (Neeper et al. 1992). The other cell surface receptors for AGEs include dolichyl-diphosphooligosaccharide-protein glycosyltransferase (AGE-R1) (Li et al. 1996), protein kinase C substrate, 80KH phosphoprotein (AGE-R2) (Goh et al. 1996), galectin-3 (AGE-R3) (Vlassara et al. 1995), and class A...

Keywords

Pentosidine Diverse Cell Type System Biology Markup Cell Type Specific Effect Standard Data Exchange 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

RAGE

Receptor for advanced glycation end products

HMGB1

High mobility group box protein 1

sRAGE

Soluble RAGE

CML

N(6)(carboxymethyl)lysine

CEL

N(6)(carboxyethyl)lysine

MMPs

Matrix metalloproteinases

PTMs

Post-translational modifications

PPIs

Protein-protein interactions

BioPAX

Biological PAthway eXchange

SBML

Systems Biology Markup Language

PSI-MI

Proteomics Standards Initiative for Molecular Interaction

Notes

Acknowledgments

We thank the Department of Biotechnology (DBT), Government of India for research support to the Institute of Bioinformatics, Bangalore. Varot K. Sandhya is a recipient of INSPIRE Fellowship from the Department of Science and Technology, Government of India. H. C. Harsha is a Wellcome Trust-DBT India Alliance Early Career Fellow.

Conflict of interests

The author(s) declared no conflicts of interests.

References

  1. Boeckmann B, Bairoch A, Apweiler R, Blatter MC, Estreicher A, Gasteiger E, Martin MJ, Michoud K, O’Donovan C, Phan I, Pilbout S, Schneider M (2003) The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res 31:365–370PubMedCrossRefGoogle Scholar
  2. Bondeva T, Wojciech S, Wolf G (2011) Advanced glycation end products inhibit adhesion ability of differentiated podocytes in a neuropilin-1-dependent manner. Am J Physiol Renal Physiol 301:F852–F870PubMedCrossRefGoogle Scholar
  3. Brett J, Schmidt AM, Yan SD, Zou YS, Weidman E, Pinsky D, Nowygrod R, Neeper M, Przysiecki C, Shaw A et al (1993) Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am J Pathol 143:1699–1712PubMedGoogle Scholar
  4. Del Turco S, Navarra T, Gastaldelli A, Basta G (2011) Protective role of adiponectin on endothelial dysfunction induced by AGEs: a clinical and experimental approach. Microvasc Res 82:73–76PubMedCrossRefGoogle Scholar
  5. Demir E, Cary MP, Paley S, Fukuda K, Lemer C, Vastrik I, Wu G et al (2010) The BioPAX community standard for pathway data sharing. Nat Biotechnol 28:935–942PubMedCrossRefGoogle Scholar
  6. Ding Q, Keller JN (2005) Splice variants of the receptor for advanced glycosylation end products (RAGE) in human brain. Neurosci Lett 373:67–72PubMedCrossRefGoogle Scholar
  7. DiNorcia J, Lee MK, Moroziewicz DN, Winner M, Suman P, Bao F, Remotti HE, Zou YS, Yan SF, Qiu W, Su GH, Schmidt AM, Allendorf JD (2012) RAGE gene deletion inhibits the development and progression of ductal neoplasia and prolongs survival in a murine model of pancreatic cancer. J Gastrointest Surg 16:104–112, discussion 112PubMedCrossRefGoogle Scholar
  8. Drinda S, Franke S, Ruster M, Petrow P, Pullig O, Stein G, Hein G (2005) Identification of the receptor for advanced glycation end products in synovial tissue of patients with rheumatoid arthritis. Rheumatol Int 25:411–413PubMedCrossRefGoogle Scholar
  9. Fritz G (2011) RAGE: a single receptor fits multiple ligands. Trends Biochem Sci 36:625–632PubMedCrossRefGoogle Scholar
  10. Goel R, Muthusamy B, Pandey A, Prasad TSK (2011a) Human protein reference database and human proteinpedia as discovery resources for molecular biotechnology. Mol Biotechnol 48:87–95PubMedCrossRefGoogle Scholar
  11. Goel R, Raju R, Maharudraiah J, Kumar GSS, Ghosh K, Kumar A, Lashmi PT et al (2011b) A signaling network of thyroid-stimulating hormone. J Proteonomics Bioinformatics 4:238–241Google Scholar
  12. Goh KC, Lim YP, Ong SH, Siak CB, Cao X, Tan YH, Guy GR (1996) Identification of p90, a prominent tyrosine-phosphorylated protein in fibroblast growth factor-stimulated cells, as 80K-H. J Biol Chem 271:5832–5838PubMedCrossRefGoogle Scholar
  13. Hamosh A, Scott AF, Amberger JS, Bocchini CA, McKusick VA (2005) Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res 33:D514–D517PubMedCrossRefGoogle Scholar
  14. Hermjakob H, Montecchi-Palazzi L, Bader G, Wojcik J, Salwinski L, Ceol A, Moore S et al (2004) The HUPO PSI’s molecular interaction format–a community standard for the representation of protein interaction data. Nat Biotechnol 22:177–183PubMedCrossRefGoogle Scholar
  15. Hu P, Lai D, Lu P, Gao J, He H (2012) ERK and Akt signaling pathways are involved in advanced glycation end product-induced autophagy in rat vascular smooth muscle cells. Int J Mol Med 29:613–618PubMedGoogle Scholar
  16. Hucka M, Finney A, Sauro HM, Bolouri H, Doyle JC, Kitano H, Arkin AP et al (2003) The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19:524–531PubMedCrossRefGoogle Scholar
  17. Kandasamy K, Keerthikumar S, Raju R, Prasad TSK, Ramachandra YL, Mohan S, Pandey A (2009) PathBuilder–open source software for annotating and developing pathway resources. Bioinformatics 25:2860–2862PubMedCrossRefGoogle Scholar
  18. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GS, Venugopal AK, Telikicherla D et al (2010) NetPath: a public resource of curated signal transduction pathways. Genome Biol 11:R3PubMedCrossRefGoogle Scholar
  19. Lander HM, Tauras JM, Ogiste JS, Hori O, Moss RA, Schmidt AM (1997) 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 272:17810–17814PubMedCrossRefGoogle Scholar
  20. Li YM, Mitsuhashi T, Wojciechowicz D, Shimizu N, Li J, Stitt A, He C, Banerjee D, Vlassara H (1996) Molecular identity and cellular distribution of advanced glycation endproduct receptors: relationship of p60 to OST-48 and p90 to 80K-H membrane proteins. Proc Natl Acad Sci U S A 93:11047–11052PubMedCrossRefGoogle Scholar
  21. Li BY, Li XL, Gao HQ, Zhang JH, Cai Q, Cheng M, Lu M (2011) Grape seed procyanidin B2 inhibits advanced glycation end product-induced endothelial cell apoptosis through regulating GSK3beta phosphorylation. Cell Biol Int 35:663–669PubMedCrossRefGoogle Scholar
  22. Liang H, Zhong Y, Zhou S, Peng L (2011) Knockdown of RAGE expression inhibits colorectal cancer cell invasion and suppresses angiogenesis in vitro and in vivo. Cancer Lett 313:91–98PubMedCrossRefGoogle Scholar
  23. Liu Y, Liang C, Liu X, Liao B, Pan X, Ren Y, Fan M, Li M, He Z, Wu J, Wu Z (2010) AGEs increased migration and inflammatory responses of adventitial fibroblasts via RAGE, MAPK and NF-kappaB pathways. Atherosclerosis 208:34–42PubMedCrossRefGoogle Scholar
  24. Logsdon CD, Fuentes MK, Huang EH, Arumugam T (2007) RAGE and RAGE ligands in cancer. Curr Mol Med 7:777–789PubMedCrossRefGoogle Scholar
  25. Ma J, Liu T, Dong X (2010) Advanced glycation end products of bovine serum albumin-induced endothelial-to-mesenchymal transition in cultured human and monkey endothelial cells via protein kinase B signaling cascades. Mol Vis 16:2669–2679PubMedGoogle Scholar
  26. Maglott D, Ostell J, Pruitt KD, Tatusova T (2005) Entrez Gene: gene-centered information at NCBI. Nucleic Acids Res 33:D54–D58PubMedCrossRefGoogle Scholar
  27. Nanjappa V, Raju R, Muthusamy B, Sharma J, Thomas K, Nidhina PAH, Harsha HC, Pandey A, Anilkumar G, Prasad TSK (2011) A comprehensive curated reaction map of leptin signaling pathway. J Proteonomics Bioinformatics 4:184–189Google Scholar
  28. Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A (1992) Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem 267:14998–15004PubMedGoogle Scholar
  29. Raju R, Balakrishnan L, Nanjappa V, Bhattacharjee M, Getnet D, Muthusamy B, Kurian Thomas J, et al. (2011) A comprehensive manually curated reaction map of RANKL/RANK-signaling pathway. Database (Oxford) 2011: bar021Google Scholar
  30. Raju R, Nanjappa V, Balakrishnan L, Radhakrishnan A, Thomas JK, Sharma J, Tian M, et al., (2011) NetSlim: high-confidence curated signaling maps. Database (Oxford) 2011: bar032Google Scholar
  31. Schmidt AM, Hasu M, Popov D, Zhang JH, Chen J, Yan SD, Brett J, Cao R, Kuwabara K, Costache G et al (1994a) 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 U S A 91:8807–8811PubMedCrossRefGoogle Scholar
  32. Schmidt AM, Hori O, Brett J, Yan SD, Wautier JL, Stern D (1994b) Cellular receptors for advanced glycation end products. Implications for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions. Arterioscler Thromb 14:1521–1528PubMedCrossRefGoogle Scholar
  33. Shimoda H, Nakamura S, Morioka M, Tanaka J, Matsuda H, Yoshikawa M (2011) Effect of Cinnamoyl and Flavonol Glucosides Derived from Cherry Blossom Flowers on the Production of Advanced Glycation End Products (AGEs) and AGE-induced Fibroblast Apoptosis. Phytother ResGoogle Scholar
  34. Sun L, Ishida T, Yasuda T, Kojima Y, Honjo T, Yamamoto Y, Yamamoto H, Ishibashi S, Hirata K, Hayashi Y (2009) RAGE mediates oxidized LDL-induced pro-inflammatory effects and atherosclerosis in non-diabetic LDL receptor-deficient mice. Cardiovasc Res 82:371–381PubMedCrossRefGoogle Scholar
  35. Takahashi HK, Zhang J, Mori S, Liu K, Wake H, Liu R, Sadamori H, Matsuda H, Yagi T, Yoshino T, Nishibori M (2010) Prostaglandin E2 inhibits advanced glycation end product-induced adhesion molecule expression on monocytes, cytokine production, and lymphocyte proliferation during human mixed lymphocyte reaction. J Pharmacol Exp Ther 334:964–972PubMedCrossRefGoogle Scholar
  36. Tanikawa T, Okada Y, Tanikawa R, Tanaka Y (2009) Advanced glycation end products induce calcification of vascular smooth muscle cells through RAGE/p38 MAPK. J Vasc Res 46:572–580PubMedCrossRefGoogle Scholar
  37. Telikicherla D, Ambekar A, Palapetta SM, Dwivedi SB, Raju R, Sharma J, Prasad TSK, Ramachandra Y, Mohan SS, Maharudraiah J, Mukherjee S, Pandey A (2011) A comprehensive curated resource for follicle stimulating hormone signaling. BMC Res Notes 4:408PubMedCrossRefGoogle Scholar
  38. Toma L, Stancu CS, Botez GM, Sima AV, Simionescu M (2009) Irreversibly glycated LDL induce oxidative and inflammatory state in human endothelial cells; added effect of high glucose. Biochem Biophys Res Commun 390:877–882PubMedCrossRefGoogle Scholar
  39. Vlassara H, Li YM, Imani F, Wojciechowicz D, Yang Z, Liu FT, Cerami A (1995) Identification of galectin-3 as a high-affinity binding protein for advanced glycation end products (AGE): a new member of the AGE-receptor complex. Mol Med 1:634–646PubMedGoogle Scholar
  40. Xie Y, You SJ, Zhang YL, Han Q, Cao YJ, Xu XS, Yang YP, Li J, Liu CF (2011) Protective role of autophagy in AGE-induced early injury of human vascular endothelial cells. Mol Med Report 4:459–464Google Scholar
  41. Xu Y, Wang S, Feng L, Zhu Q, Xiang P, He B (2010) Blockade of PKC-beta protects HUVEC from advanced glycation end products induced inflammation. Int Immunopharmacol 10:1552–1559PubMedCrossRefGoogle Scholar
  42. Yamagishi S (2011) Role of advanced glycation end products (AGEs) and receptor for AGEs (RAGE) in vascular damage in diabetes. Exp Gerontol 46:217–224PubMedCrossRefGoogle Scholar
  43. Yan SF, Ramasamy R, Schmidt AM (2009) Receptor for AGE (RAGE) and its ligands-cast into leading roles in diabetes and the inflammatory response. J Mol Med (Berl) 87:235–247CrossRefGoogle Scholar
  44. Yoon SJ, Yoon YW, Lee BK, Kwon HM, Hwang KC, Kim M, Chang W, Hong BK, Lee YH, Park SJ, Min PK, Rim SJ (2009) Potential role of HMG CoA reductase inhibitor on oxidative stress induced by advanced glycation endproducts in vascular smooth muscle cells of diabetic vasculopathy. Exp Mol Med 41:802–811PubMedCrossRefGoogle Scholar
  45. Yuan X, Zhang Z, Gong K, Zhao P, Qin J, Liu N (2011) Inhibition of reactive oxygen species/extracellular signal-regulated kinases pathway by pioglitazone attenuates advanced glycation end products-induced proliferation of vascular smooth muscle cells in rats. Biol Pharm Bull 34:618–623PubMedCrossRefGoogle Scholar

Copyright information

© The International CCN Society 2012

Authors and Affiliations

  • Sowmya Soman
    • 1
  • Rajesh Raju
    • 1
  • Varot K. Sandhya
    • 1
  • Jayshree Advani
    • 1
  • Aafaque Ahmad Khan
    • 1
  • H. C. Harsha
    • 1
  • T. S. Keshava Prasad
    • 1
  • P. R. Sudhakaran
    • 2
  • Akhilesh Pandey
    • 3
    • 4
    • 5
    • 6
  • Puneeth K. Adishesha
    • 1
  1. 1.Institute of BioinformaticsInternational Technology ParkBangaloreIndia
  2. 2.Department of Computational Biology and Bioinformatics, State Inter-University Centre of Excellence in BioinformaticsUniversity of KeralaThiruvananthapuramIndia
  3. 3.McKusick-Nathans Institute of Genetic MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  4. 4.Department of Biological ChemistryJohns Hopkins University School of MedicineBaltimoreUSA
  5. 5.Department of OncologyJohns Hopkins University School of MedicineBaltimoreUSA
  6. 6.Department of PathologyJohns Hopkins University School of MedicineBaltimoreUSA

Personalised recommendations