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

  • Authors:
    • Endy Widya Putranto
    • Hitoshi Murata
    • Ken‑Ichi Yamamoto
    • Ken Kataoka
    • Hidenori Yamada
    • Jun‑Ichiro Futami
    • Masakiyo Sakaguchi
    • Nam‑Ho Huh
  • View Affiliations

  • Published online on: August 9, 2013     https://doi.org/10.3892/ijmm.2013.1467
  • Pages: 938-944
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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 β. 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.
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October 2013
Volume 32 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Putranto EW, Murata H, Yamamoto KI, Kataoka K, Yamada H, Futami JI, Sakaguchi M and Huh NH: Inhibition of RAGE signaling through the intracellular delivery of inhibitor peptides by PEI cationization. Int J Mol Med 32: 938-944, 2013
APA
Putranto, E.W., Murata, H., Yamamoto, K., Kataoka, K., Yamada, H., Futami, J. ... Huh, N. (2013). Inhibition of RAGE signaling through the intracellular delivery of inhibitor peptides by PEI cationization. International Journal of Molecular Medicine, 32, 938-944. https://doi.org/10.3892/ijmm.2013.1467
MLA
Putranto, E. W., Murata, H., Yamamoto, K., Kataoka, K., Yamada, H., Futami, J., Sakaguchi, M., Huh, N."Inhibition of RAGE signaling through the intracellular delivery of inhibitor peptides by PEI cationization". International Journal of Molecular Medicine 32.4 (2013): 938-944.
Chicago
Putranto, E. W., Murata, H., Yamamoto, K., Kataoka, K., Yamada, H., Futami, J., Sakaguchi, M., Huh, N."Inhibition of RAGE signaling through the intracellular delivery of inhibitor peptides by PEI cationization". International Journal of Molecular Medicine 32, no. 4 (2013): 938-944. https://doi.org/10.3892/ijmm.2013.1467