Identification of mouse orthologue of endogenous secretory receptor for advanced glycation end-products: structure, function and expression.
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-kappaB (nuclear factor kappaB) 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.
Harashima
Ai
A
Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Yamamoto
Yasuhiko
Y
Cheng
Chunmei
C
Tsuneyama
Koichi
K
Myint
Khin Mar
KM
Takeuchi
Akihiko
A
Yoshimura
Kazunobu
K
Li
Hui
H
Watanabe
Takuo
T
Takasawa
Shin
S
Okamoto
Hiroshi
H
Yonekura
Hideto
H
Yamamoto
Hiroshi
H
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005910:Glioma / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D013045:Species Specificity; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance; D014162:Transfection
D017127:Glycation End Products, Advanced; D008024:Ligands; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic