Mitocryptide-2, a neutrophil-activating cryptide, is a specific endogenous agonist for formyl-peptide receptor-like 1

Seki, Tetsuo; Fukamizu, Akiyoshi; Kiso, Yoshiaki; Mukai, Hidehito

doi:10.1016/j.bbrc.2010.12.007

Cited by 23 publications

(24 citation statements)

References 32 publications

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“…Cryptides are endogenous, fragmented functional peptides. Pro-inflammatory cryptides from mtDNA and nuclear DNA-encoded mitochondrial proteins were recently described (153–155). As reviewed in Table 1, each of these molecules has been observed to initiate a pro-inflammatory phenotype under various disease and pathological states.…”

Section: Mitochondria-derived Damps: Inducers Of Neuroinflammation?mentioning

confidence: 99%

Mitochondria-Derived Damage-Associated Molecular Patterns in Neurodegeneration

et al. 2017

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Inflammation is increasingly implicated in neurodegenerative disease pathology. As no acquired pathogen appears to drive this inflammation, the question of what does remains. Recent advances indicate damage-associated molecular pattern (DAMP) molecules, which are released by injured and dying cells, can cause specific inflammatory cascades. Inflammation, therefore, can be endogenously induced. Mitochondrial components induce inflammatory responses in several pathological conditions. Due to evidence such as this, a number of mitochondrial components, including mitochondrial DNA, have been labeled as DAMP molecules. In this review, we consider the contributions of mitochondrial-derived DAMPs to inflammation observed in neurodegenerative diseases.

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Section: Mitochondria-derived Damps: Inducers Of Neuroinflammation?mentioning

confidence: 99%

Mitochondria-Derived Damage-Associated Molecular Patterns in Neurodegeneration

et al. 2017

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“…Mitocryptide-2 (MCT-2) is a soluble pentadecapeptide (formyl-MTNIRKSHPLMKIIN), produced from mitochondrial cytochrome b , whose N-terminus is formylated [18]. MCT-2 efficiently induces migration and activation of peripheral neutrophils, as well as of neutrophilic/granulocytic cells differentiated from HL-60 cells and promotes phosphorylation of ERK1/2 and an increase in intracellular Ca 2+ concentration by binding to FPR2 [18].…”

Section: Endogenous Peptidesmentioning

confidence: 99%

“…MCT-2 efficiently induces migration and activation of peripheral neutrophils, as well as of neutrophilic/granulocytic cells differentiated from HL-60 cells and promotes phosphorylation of ERK1/2 and an increase in intracellular Ca 2+ concentration by binding to FPR2 [18]. These signaling events are largely prevented by cells pretreated with pertussis toxin (PTX), which ADP-ribosylates G i - and G o -type G-proteins and renders them insensitive to receptor regulation.…”

Section: Endogenous Peptidesmentioning

confidence: 99%

“…Moreover, in neutrophilic/granulocytic cells, MCT-2 induces β-hexosaminidase release, which is a glycosidase that is released from neutrophilic cells upon stimulation of their activating factors. The enzyme release promoted by MCT-2 is completely inhibited by PTX treatment [18]. The observation that FPR2 specifically and efficiently recognizes cryptide MCT-2 suggests that many peptides produced by the degradation of functional proteins may be associated with unidentified physiological regulations (Table 2).…”

Section: Endogenous Peptidesmentioning

confidence: 99%

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Distinct Signaling Cascades Elicited by Different Formyl Peptide Receptor 2 (FPR2) Agonists

Cattaneo

Parisi

Ammendola

2013

IJMS

147

158

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The formyl peptide receptor 2 (FPR2) is a remarkably versatile transmembrane protein belonging to the G-protein coupled receptor (GPCR) family. FPR2 is activated by an array of ligands, which include structurally unrelated lipids and peptide/proteins agonists, resulting in different intracellular responses in a ligand-specific fashion. In addition to the anti-inflammatory lipid, lipoxin A4, several other endogenous agonists also bind FPR2, including serum amyloid A, glucocorticoid-induced annexin 1, urokinase and its receptor, suggesting that the activation of FPR2 may result in potent pro- or anti-inflammatory responses. Other endogenous ligands, also present in biological samples, include resolvins, amyloidogenic proteins, such as beta amyloid (Aβ)-42 and prion protein (Prp)106–126, the neuroprotective peptide, humanin, antibacterial peptides, annexin 1-derived peptides, chemokine variants, the neuropeptides, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP)-27, and mitochondrial peptides. Upon activation, intracellular domains of FPR2 mediate signaling to G-proteins, which trigger several agonist-dependent signal transduction pathways, including activation of phospholipase C (PLC), protein kinase C (PKC) isoforms, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, the mitogen-activated protein kinase (MAPK) pathway, p38MAPK, as well as the phosphorylation of cytosolic tyrosine kinases, tyrosine kinase receptor transactivation, phosphorylation and nuclear translocation of regulatory transcriptional factors, release of calcium and production of oxidants. FPR2 is an attractive therapeutic target, because of its involvement in a range of normal physiological processes and pathological diseases. Here, we review and discuss the most significant findings on the intracellular pathways and on the cross-communication between FPR2 and tyrosine kinase receptors triggered by different FPR2 agonists.

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“…Their function is not entirely clear, but they are believed to act as mtDAMPs and promote phagocytosis and other innate immune protection mechanisms during cellular or tissue injury, but also may take part in sterile inflammation development. A cryptide MCT-2 seems to be particularly interesting, because it is a selective FPRL1 agonist and does not activate FPR (Seki et al, 2011). MCT-2 is a fragment of mitochondrial cytochrome b containing N-terminal formyl-methionine residue and 14 other amino acids (Mukai et al, 2009).…”

Section: Receptors Binding Mitochondrial Peptidesmentioning

confidence: 99%