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Article

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 / Copyright

    Affiliations: Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan, Department of Life Science, Faculty of Science, Okayama University of Science, Okayama 700‑0005, Japan, Department of Medical Bioengineering Science, Okayama University Graduate School of Natural Science and Biotechnology, Okayama 700‑8530, Japan
  • Pages: 938-944
    |
    Published online on: August 9, 2013
       https://doi.org/10.3892/ijmm.2013.1467
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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