Isolation and Identification of Novel Neutrophil-Activating Cryptides Hidden in Mitochondrial Cytochrome c

Authors: Hokari, Yoshinori; Seki, Tetsuo; Nakano, Hiroko; Matsuo, Yuko; Fukamizu, Akiyoshi; Munekata, Eisuke; Kiso, Yoshiaki; Mukai, Hidehito

Source: Protein and Peptide Letters, Volume 19, Number 6, June 2012 , pp. 680-687(8)

Publisher: Bentham Science Publishers

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Abstract:

Although it is known that neutrophils infiltrate damaged sites immediately after tissue injury, the endogenous factors that induce their acute transmigration and activation have not been thoroughly investigated. For the candidates of those factors, we recently discovered two novel neutrophil-activating cryptides, mitocryptide-1 (MCT-1) and mitocryptide-2 (MCT-2), hidden in mitochondrial proteins. In addition, many unknown neutrophil-activating peptides other than MCT-1 and MCT-2 were also observed during their purification. Here, we isolated and purified a novel neutrophil-activating peptide from porcine hearts, which we showed by structural analyses to have an identical primary structure to porcine mitochondrial cytochrome c (68-85). We named this novel functional octadecapeptide as mitocryptide-CYC (MCT-CYC). Structure-activity relationships of cytochrome c on β-hexosaminidase (β-HA) release from neutrophilic-differentiated HL- 60 cells demonstrated that peptides derived from the C-terminal part of cytochrome c induced β-HA release and that cytochrome c (70-85) was the most potent cryptide among them. Since cytochrome c is known to be involved in the apoptotic process, our results suggest that cryptides, including MCT-CYC, derived from mitochondrial cytochrome c are possible factors that induce scavenging of toxic debris produced from apoptotic cells by neutrophils.

Keywords: Cryptide; cytochrome c; mitochondria; mitocryptide-1; mitocryptide-2; mitocryptide-CYC; neutrophil; arboxypeptidases; neutrophil-activating peptide; Peptidergic neurotransmitters

Document Type: Research article

DOI: http://dx.doi.org/10.2174/092986612800494048

Affiliations: 1: Laboratory of Peptide Science, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan.

Publication date: 2012-06-01

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Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.

Isolation and Identification of Novel Neutrophil-Activating Cryptides Hidden in Mitochondrial Cytochrome c

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