Abstract
Purified human brain neurofilament protein was subjected to glycating conditions to produce an advanced glycation end product (HNF-AGE). Two mice were immunized with this HNF-AGE. Unexpectedly, the animals generated IgGs against a peptide immunogenic fragment of the receptor for advanced glycation end products (RAGE) and against human amyloid β peptide (Aβ). In leukocyte populations, 30–52% of lymphocytes were positive for cell-surface RAGE, and 20–25% were positive for the Aβ peptide. A monoclonal antibody (MAb) directed against the sequence of human RAGE was reactive against a 35-kDa protein band that was highly expressed in blood cells, plasma proteins, lung, liver, spleen, and brain derived from the immunized mice. A MAb directed against Aβ proteins also identified the same 35-kDa band. Thus, the time-dependent formation of AGEs might play a role within the context of the immune system in the expression of binding sites for amyloid peptides, possibly resulting in enhancing cellular toxicity.
Similar content being viewed by others
References
Balin B. J. and Lee V. M. (1991) Individual neurofilament subunits reassembled in vitro exhibit unique biochemical, morphological and immunological properties. Brain Res. 556, 196–208.
Balin B. J., Clark E. A., Trojanowski J. Q., and Lee V. M. (1991) Neurofilament reassembly in vitro: biochemical, morphological and immuno-electron microscopic studies employing monoclonal antibodies to defined epitopes. Brain Res. 556, 181–195.
Benzi G. and Moretti A. (1995) Are reactive oxygen species involved in Alzheimer’s disease? Neurobiol. Aging 16, 661–674.
Brett J., Schmidt A. M., Yan S. D., Zou Y. S., Weidman E., Pinsky D., et al. (1993) Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am. J. Pathol. 143, 1699–1712.
Castellani R., Smith M. A., Richey P. L., and Perry G. (1996) Glycoxidation and oxidative stress in Parkinson disease and diffuse Lewy body disease. Brain Res. 737, 195–200.
DeMattos R. B., Bales K. R., Cummins D. J., Paul S. M., and Holtzman D. M. (2002) Brain to plasma amyloid-β efflux: a measure of brain amyloid burden in a mouse model of Alzheimer’s disease. Science 295, 2264–2267.
Halliday G., Robinson S. R., Shepherd C., and Kril J. (2000) Alzheimer’s disease and inflammation: a review of cellular and therapeutic mechanisms. Clin. Exp. Pharmacol. Physiol. 27, 1–8.
Horiuchi S., Araki N., and Morino Y. (1991) Immunochemical approach to characterize advanced glycation end products of the Millard reaction; Evidences for the presence of a common structure. J. Biol. Chem. 266, 7329–7332.
Jung S. S., Gautheir S., and Cashman N. R. (1999) Beta amyloid precursor protein is detectable on monocytes and is increased in Alzheimer’s disease. Neurobiol. Aging 3, 249–257.
Khechai F., Ollivier V., Bridey F., Amar M., Hakim J., and de Prost D. (1997) Effect of advanced glycation end product-modified albumin on tissue factor expression by monocytes. Role of oxidant stress and protein tyrosine kinase activation. Arterioscler. Thromb. Vasc. Biol. 17, 2885–2890.
Ko L.-W., Ko E. C., Nacharaju P., Liu W.-K., Chang E., Kenessey A., and Yen S.-H. C. (1999) An immunochemical study on tau glycation in paired helical filaments. Brain Res. 830, 301–313.
Lopez O. L., Rabin B. S., and Huff F. J. (1991) Serum autoantibodies in Alzheimer’s disease. Acta Neurol. Scand. 84, 441–444.
Makita Z., Vlassara H., Cerami A., and Bucala R. (1992) Immunochemical detection of advanced glycosylation end products in vivo. J. Biol. Chem. 267, 5133–5138.
Marx F., Blasko I., Pavelka M., and Grubeck-Loebenstein B. (1998) The possible role of the immune system in Alzheimer’s disease. Exp. Gerontol. 33, 871–881.
Mattson M. P. (1997) Central role of oxyradicals in the mechanism of amyloid β-peptide cytotoxicity. Alzheimer’s Dis. Rev. 2, 1–14.
McGeer P. L., McGeer E. G., Kawamata T., Yamada T., and Akiyama H. (1991) Reactions of the immune system in chronic degenerative neurological diseases. Can. J. Neurolog. Sci. 18(3 Suppl), 376–379.
Miranda S., Opazo C., Larrondo L. F., Munoz F. J., Ruiz F., Leighton F., and Inestrosa N. C. (2000) The role of oxidative stress in the toxicity induced by amyloid beta-peptide in Alzheimer’s disease. Prog. Neurobiol. 6, 633–648.
Mruthinti S., Jilani Y. I., Hill W. D., and Buccafusco J. J. (2000) Glycated albumin enhances the binding of amyloid peptide fragment (Aβ1-42) to PC-12 cells. Society Neurosci. Abstr. 26, 1786.
Münch G., Luth H. J., Wong A., Arendt T., Hirsch E., Ravid R., and Riederer P. (2000) Crosslinking of alpha-synuclein by advanced glycation endproducts—an early pathophysiological step in Lewy body formation? J. Chem. Neuroanat. 20, 253–257.
Münch G., Simm A., Double K. L., and Riederer P. (1996) Oxidative stress and advanced glycation end products—parts of a vicious circle of neurodegeneration. Alzheimer’s Dis. Rev. 1, 71–74.
Myagkova M. A., Gavrilova S. I., Lermontova N. N., Kalyn Y. B., Selezneva N. D., Zharikov G. A., et al. (2001) Autoantibodies to beta-amyloid and neurotransmitters in patients with Alzheimer’s disease and senile dementia of the Alzheimer type. Bull. Exp. Biol. Med. 131, 127–129.
Neeper M., Schmidt A. M., Brett J., Yan S. D., Wang F., Pan Y. C., et al. (1992) Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J. Biol. Chem. 267, 14,998–15,004.
Nicolau C., Greferath R., Balaban T. S., Lazarte J. E., and Hopkins R. J. (2002) A liposome-based therapeutic vaccine against β-amyloid plaques on the pancreas of transgenic NORBA mice. Proc. Natl. Acad. Sci. USA 99, 2332–2337.
Niwa T. (2001) Dialysis-related amyloidosis: pathogenesis focusing on AGE modification. Semin. Dialysis 14, 123–126.
Ott A., Stolk R. P., Hofman A., van Harskamp F., Grobbee D. E., and Breteler M. M. (1996) Association of diabetes mellitus and dementia: the Rotterdam study. Diabetologia 39, 1392–1397.
Sasaki N., Toki S., Chowei H., Toshikazu S., Nakano N., Hayashi Y., et al. (2001) Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer’s disease. Brain Res. 888, 256–262.
Schenk D., Barbour R., Dunn W., et al. (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400, 173–177.
Schmidt A. M., Yan S. D., Yan S. F., and Stern D. M. (2000) The biology of the receptor for advanced glycation end products and its ligands. Biochim. Biophys. Acta. 1498, 99–111.
Shyamala M., Kiefer C. R., Moscoso H., and Garver F. A. (1992) A monoclonal antibody-linked immunoassay for hemoglobin H disease. Ann. Hematol. 65, 37–40.
Smith M. A., Taneda S., Richey P. L., Miyata S., Yan S. D., Stern D., et al. (1994) Advanced Maillard reaction end products are associated with Alzheimer disease pathology. Proc. Natl. Acad. Sci. USA 91, 5710–5714.
Stewart R. and Liolitsa D. (1999) Type 2 diabetes mellitus, cognitive impairment and dementia. Diabetic Med. 16, 93–112.
Subbarao K., Richardson J., and Ang L. (1990) Autopsy samples of Alzheimer’s cortex show increased peroxidation in vitro. J. Neurochem. 55, 342–345.
Terryberry J. W., Thor G., and Peter J. P. (1998) Autoantibodies in neurodegenerative disease: antigen-specific frequencies and intrathecal analysis. Neurobiol. Aging 19, 205–216.
Town T., Tan J., Sansone N., Obregon D., Klein T., and Mullan M. (2001) Characterization of murine immunoglobulin G antibodies against human amyloid-β1–42. Neurosci. Lett. 307, 101–104.
Yan S. D., Roher A., Chaney M., Zlokovic B., Schmidt A. M., and Stern D. (2000) Cellular cofactors potentiating induction of stress and cytotoxicity by amyloid beta-peptide. Biochim. Biophys. Acta 1502, 145–157.
Yan S. D., Stern D., Kane M. D., Kuo Y. M., Lampert H. C., and Roher A. E. (1998) RAGE-A beta interactions in the pathophysiology of Alzheimer’s disease. Restorative Neurol. Neurosci. 12, 167–173.
Yan S. D., Yan S. F., Chen X., Fu J., Chen M., Kuppusamy P., et al. (1995) Non-enzymatically glycated tau in Alzheimer’s disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid beta-peptide. Nat. Med. 1, 693–699.
Yan S. D., Zhu H., Fu J., Yan S. F., Roher A., Tourtellottee W. W., et al. (1997) Amyloid-beta peptide-receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: a proinflammatory pathway in Alzheimer disease. Proc. Natl. Acad. Sci. USA 94, 5296–5301.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mruthinti, S., Hill, W.D., Swamy-Mruthinti, S. et al. Relationship between the induction of RAGE cell-surface antigen and the expression of amyloid binding sites. J Mol Neurosci 20, 223–232 (2003). https://doi.org/10.1385/JMN:20:3:223
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/JMN:20:3:223