このエントリーをはてなブックマークに追加
ID 52412
FullText URL
Author
Putranto, Endy Widya
Yamamoto, Ken-Ichi
Kataoka, Ken
Yamada, Hidenori
Abstract
The receptor for advanced glycation end products (RAGE) is a multi-ligand cell surface receptor and a member of the immunoglobulin superfamily. RAGE is involved in a wide range of inflammatory, degenerative and hyper-proliferative disorders which span over different organs by engaging diverse ligands, including advanced glycation end products, S100 family proteins, high-mobility group protein B1 (HMGB1) and amyloid beta. We previously demonstrated that the cytoplasmic domain of RAGE is phosphorylated upon the binding of ligands, enabling the recruitment of two distinct pairs of adaptor proteins, Toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP) and myeloid differentiation protein 88 (MyD88). This engagement allows the activation of downstream effector molecules, and thereby mediates a wide variety of cellular processes, such as inflammatory responses, apoptotic cell death, migration and cell growth. Therefore, inhibition of the binding of TIRAP to RAGE may abrogate intracellular signaling from ligand-activated RAGE. In the present study, we developed inhibitor peptides for RAGE signaling (RAGE-I) by mimicking the phosphorylatable cytosolic domain of RAGE. RAGE-I was efficiently delivered into the cells by polyethylenimine (PEI) cationization. We demonstrated that RAGE-I specifically bound to TIRAP and abrogated the activation of Cdc42 induced by ligand-activated RAGE. Furthermore, we were able to reduce neuronal cell death induced by an excess amount of S100B and to inhibit the migration and invasion of glioma cells in vitro. Our results indicate that RAGE-I provides a powerful tool for therapeutics to block RAGE-mediated multiple signaling.
Keywords
receptor for advanced glycation end products
Toll-interleukin 1 receptor domain-containing adaptor protein
cationization
S100B
cell death
cell migration
Published Date
2013-10
Publication Title
International Journal of Molecular Medicine
Volume
volume32
Issue
issue4
Publisher
Spandidos Publications Ltd.
Start Page
938
End Page
944
ISSN
1107-3756
NCID
AA11445762
Content Type
Journal Article
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/52249
language
英語
File Version
publisher
DOI
Web of Sience KeyUT