Biochem. J. (2006) 396
(109–115) (Printed in Great Britain)
Identification of mouse orthologue of endogenous secretory receptor for advanced glycation end-products: structure, function and expression
Ai HARASHIMA*, Yasuhiko YAMAMOTO*1, Chunmei CHENG†, Koichi TSUNEYAMA†, Khin Mar MYINT*, Akihiko TAKEUCHI*, Kazunobu YOSHIMURA*, Hui LI*, Takuo WATANABE*, Shin TAKASAWA‡, Hiroshi OKAMOTO§, Hideto YONEKURA* and Hiroshi YAMAMOTO*
*Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan, †Department of Pathology, School of Medicine, University of Toyama, Toyama 930-0194, Japan, ‡Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan, and §Department of Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories), Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
The cell-surface RAGE [receptor for AGE (advanced glycation end-products)] is associated with the development of diabetic vascular complications, neurodegenerative disorders and inflammation. Recently, we isolated a human RAGE splice variant, which can work as a decoy receptor for RAGE ligands, and named it esRAGE (endogenous secretory RAGE). In the present study, we have isolated the murine equivalent of esRAGE from brain polysomal poly(A)+ (polyadenylated) RNA by RT (reverse transcription)–PCR cloning. The mRNA was generated by alternative splicing, and it encoded a 334-amino-acid protein with a signal sequence, but lacking the transmembrane domain. A transfection experiment revealed that the mRNA was actually translated as deduced to yield the secretory protein working as a decoy in AGE-induced NF-kB (nuclear factor kB) activation. RT–PCR and immunoblotting detected esRAGE mRNA and protein in the brain, lung, kidney and small intestine of wild-type mice, but not of RAGE-null mice. The esRAGE expression was increased in the kidney of diabetic wild-type mice. The present study has thus provided an animal orthologue of esRAGE for clarification of its roles in health and disease.
Key words: advanced glycation end-product, endogenous secretory receptor for advanced glycation end-products (esRAGE), immunohistochemistry, reverse transcription–PCR cloning.
Abbreviations used: AGE, advanced glycation end-products; DMEM, Dulbecco's modified Eagle's medium; esRAGE, endogenous secretory receptor for AGE; FBS, foetal bovine serum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; NF-kB, nuclear factor kB; poly(A)+, polyadenylated; RAGE, receptor for AGE; RT, reverse transcription; RU, response units; SPR, surface plasmon resonance; sRAGE, soluble form of RAGE.
1To whom correspondence should be addressed (email yasuyama@med.kanazawa-u.ac.jp).
The nucleotide sequence data reported for mouse endogenous secretory receptor for advanced glycation end-products appear in the DDBJ, EMBL, GenBank® and GSDB Nucleotide Sequence Databases under the accession number AB207883.
Received 23 September 2005/9 February 2006; accepted 28 February 2006
Published as BJ Immediate Publication 28 February 2006, doi:10.1042/BJ20051573
The Biochemical Society, London ©2006
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