Papers

Peer-reviewed
Oct, 2013

Inhibition of RAGE signaling through the intracellular delivery of inhibitor peptides by PEI cationization

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
  • Endy Widya Putranto
  • ,
  • Hitoshi Murata
  • ,
  • Ken-Ichi Yamamoto
  • ,
  • Ken Kataoka
  • ,
  • Hidenori Yamada
  • ,
  • Jun-Ichiro Futami
  • ,
  • Masakiyo Sakaguchi
  • ,
  • Nam-Ho Huh

Volume
32
Number
4
First page
938
Last page
944
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.3892/ijmm.2013.1467
Publisher
SPANDIDOS PUBL LTD

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.

Link information
DOI
https://doi.org/10.3892/ijmm.2013.1467
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23934084
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000323725200025&DestApp=WOS_CPL
ID information
  • DOI : 10.3892/ijmm.2013.1467
  • ISSN : 1107-3756
  • Pubmed ID : 23934084
  • Web of Science ID : WOS:000323725200025

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