Oral Presentation 5th Modern Solid Phase Peptide Synthesis Symposium 2015

Mitocryptides: Structure-activity relationships of a novel family of neutrophil-activating peptides (#13)

Hidehito Mukai 1 , Takayuki Marutani 1 , Koki Tsutsumi 1 , Kenta Nakashima 1 , Tatsuya Hattori 1 , Yoshiaki Kiso 1
  1. Nagahama Institute of Bio-Science and Technology, Nagahama, Japan

Cryptides are bioactive peptides produced by proteolysis during maturation and degradation processes of functional proteins [1]. Their cellular signaling mechanisms have been investigated and it was demonstrated the presence of their own receptor molecules. Therefore, it has been paid attention to the physiological roles of those cryptides as non-classical bioactive peptides.

It is well known that neutrophils transmigrate into damaged tissues from bloodstream when bacterial infection or internal tissue injury occurs. However, it is still uncertain what factors induce the initial neutrophil migration. For the candidates, we have purified and identified three novel neutrophil-activating cryptides, mitocryptide-1 (MCT-1), mitocryptide-2 (MCT-2), and mitocryptide-CYC, which were derived from mitochondrial cytochrome c oxidase subunit VIII, cytochrome b, and cytochrome c, respectively, from healthy porcine hearts [1-4]. However, physiological roles of those cryptides and their involvements in various diseases associated with the neutrophilic infiltration have not been elucidated yet.

Here, we investigated ligand recognition mechanisms of receptor molecules for mitocryptides by studying structure-activity relationships of mitocryptides in order to elucidate signaling mechanisms of neutrophils induced by mitocryptides. We also discuss about physiological and pathophysiological significance of those mitocryptides [5].

  1. Ueki, N., Someya, K., Matsuo, Y., Wakamatsu, K., Mukai, H. (2007) Biopolymers (Pep. Sci.), 88, 190–198.
  2. Mukai, H., Hokari, Y., Seki, T., Takao, T., Kubota, M., Matsuo, Y., Tsukagoshi, H., Kato, M., Kimura, H., Shimonishi, Y., Kiso, Y., Nishi, Y., Wakamatsu, K., Munekata, E. (2008) J. Biol. Chem., 283, 30596–30605.
  3. Mukai, H., Seki, T., Nakano, H., Hokari, Y., Takao, T., Kawanami, M., Tsukagoshi, H., Kimura, H., Kiso, Y., Shimonishi, Y., Nishi, Y., Munekata, E. (2009) J. Immunol., 182, 5072–5080.
  4. Hokari, Y., Seki, T., Nakano, H., Matsuo, Y., Fukamizu, A., Munekata, E., Kiso, Y., Mukai, H. (2012) Prot. Pept. Lett., 19, 680–687.
  5. Hattori, T., Nakashima, K., Marutani, T., Kiso, Y., Nishi, Y., Mukai, H. (2015) Biochem. Biophys. Res. Commun., 463, 54-59.