Discovery of mitocryptide-1, a neutrophil-activating cryptide from healthy porcine heart.

Abstract

Although neutrophils are known to migrate in response to various chemokines and complement factors, the substances involved in the early stages of their transmigration and activation have been poorly characterized to date. Here we report the discovery of a peptide isolated from healthy porcine hearts that activated neutrophils. Its primary structure is H-Leu-Ser-Phe-Leu-Ile-Pro-Ala-Gly-Trp-Val-Leu-Ser-His-Leu-Asp-His-Tyr-Lys-Arg-Ser-Ser-Ala-Ala-OH, and it was indicated to originate from mitochondrial cytochrome c oxidase subunit VIII. This peptide caused chemotaxis at concentrations lower than that inducing beta-hexosaminidase release. Such responses were observed in neutrophilic/granulocytic differentiated HL-60 cells but not in undifferentiated cells, and G(i2)-type G proteins were suggested to be involved in the peptide signaling. Moreover the peptide activated human neutrophils to induce beta-hexosaminidase secretion. A number of other amphipathic neutrophil-activating peptides presumably originating from mitochondrial proteins were also found. The present results suggest that neutrophils monitor such amphipathic peptides including the identified peptide as an initiation signal for inflammation at injury sites.

• Authors: Hidehito Mukai, Yoshinori Hokari, Tetsuo Seki, Toshifumi Takao, Makoto Kubota, Yuko Matsuo, Hiroyuki Tsukagoshi, Masahiko Kato, Hirokazu Kimura, Yasutsugu Shimonishi, Yoshiaki Kiso, Yoshisuke Nishi, Kaori Wakamatsu, Eisuke Munekata
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 283 Issue 45 Pg. 30596-605 (Nov 07 2008) ISSN: 0021-9258 [Print] United States
• PMID: 18768476 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mitochondrial Proteins
• Muscle Proteins
• Peptides
• Electron Transport Complex IV
• beta-N-Acetylhexosaminidases

Topics

• Animals
• Chemotaxis (drug effects)
• Electron Transport Complex IV (chemistry, isolation & purification, pharmacology)
• HL-60 Cells
• Humans
• Mitochondrial Proteins (chemistry, isolation & purification, pharmacology)
• Muscle Proteins (chemistry, isolation & purification, pharmacology)
• Myocardium (chemistry)
• Neutrophil Activation (drug effects)
• Neutrophils (metabolism)
• Peptides (chemistry, isolation & purification, pharmacology)
• Swine
• beta-N-Acetylhexosaminidases (metabolism)