IntJMolMed_32_4_938-944.pdf 939 KB
Putranto, Endy Widya Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol
Murata, Hitoshi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol Kaken ID publons researchmap
Yamamoto, Ken-Ichi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol
Kataoka, Ken Okayama Univ Sci, Fac Sci, Dept Life Sci
Yamada, Hidenori Okayama Univ, Grad Sch Nat Sci & Biotechnol, Dept Med Bioengn Sci
Futami, Jun-Ichiro Okayama Univ, Grad Sch Nat Sci & Biotechnol, Dept Med Bioengn Sci ORCID Kaken ID publons researchmap
Sakaguchi, Masakiyo Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol ORCID Kaken ID publons researchmap
Huh, Nam-Ho Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Biol
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.
receptor for advanced glycation end products
Toll-interleukin 1 receptor domain-containing adaptor protein
International Journal of Molecular Medicine
Spandidos Publications Ltd.
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