Non-disulfide-bridged peptides from Tityus serrulatus venom: Evidence for proline-free ACE-inhibitors

Pucca, Manuela Berto; Cerni, Felipe Augusto; Pinheiro-Júnior, Ernesto Lopes; Zoccal, Karina Furlani; Bordon, Karla de Castro Figueiredo; Amorim, Fernanda Gobbi; Peigneur, Steve; Vriens, Kim; Thevissen, Karin; Cammue, Bruno Philippe Angelo; Martins, Ronaldo Teixeira; Arruda, Eurico; Faccioli, Lúcia Helena; Tytgat, Jan; Arantes, Eliane Candiani

doi:10.1016/j.peptides.2016.05.008

Cited by 14 publications

(11 citation statements)

References 47 publications

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“…Remarkably, the alternative phenotype of P17-treated h-MDMs is accompanied by an inflammatory signature characterized by IL-1β and ROS productions. In line, previous studies have highlighted the capacity of HDPs to simultaneously promote pro-inflammatory response while protecting host organism against exacerbated inflammatory response ( 18 , 25 , 26 , 61 – 64 ). Consistent with the increased IL-1β production in P17-treated h-MDMs, the processing of pro-caspase-1 into its p20 subunit, which is a hallmark of caspase-1 activation ( 65 ), is augmented in P17-treated h-MDMs.…”

Section: Discussionsupporting

confidence: 71%

“…This human cathelicidin is also involved in immune cells apoptosis, angiogenesis, and wound-healing regulation ( 20 – 24 ). Similar to LL-37, immunomodulatory effects on innate immunity were also described for defensins and several HDPs found in insect venom ( 25 , 26 ). Usually, their effects on immune cells are mediated through G-protein-coupled receptors (GPCRs).…”

Section: Introductionmentioning

confidence: 60%

“…Altogether these properties confer to LL-37 a strong microbicidal activity through its involvement in the control of inflammatory and anti-infectious signaling in macrophages. These immunomodulatory functions on human and murine cells are also described for HDPs from arthropods, such as apidaecin, bee venom AMP, and venom peptides 7.2 and 7.8, parabutoporin and opistoporin, isolated from scorpion venom ( 25 , 26 , 55 ). Our team has recently isolated a new short HDP from T. bicarinatum ant venom, called P17.…”

Section: Discussionmentioning

confidence: 78%

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P17, an Original Host Defense Peptide from Ant Venom, Promotes Antifungal Activities of Macrophages through the Induction of C-Type Lectin Receptors Dependent on LTB4-Mediated PPARγ Activation

et al. 2017

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Despite the growing knowledge with regard to the immunomodulatory properties of host defense peptides, their impact on macrophage differentiation and on its associated microbicidal functions is still poorly understood. Here, we demonstrated that the P17, a new cationic antimicrobial peptide from ant venom, induces an alternative phenotype of human monocyte-derived macrophages (h-MDMs). This phenotype is characterized by a C-type lectin receptors (CLRs) signature composed of mannose receptor (MR) and Dectin-1 expression. Concomitantly, this activation is associated to an inflammatory profile characterized by reactive oxygen species (ROS), interleukin (IL)-1β, and TNF-α release. P17-activated h-MDMs exhibit an improved capacity to recognize and to engulf Candida albicans through the overexpression both of MR and Dectin-1. This upregulation requires arachidonic acid (AA) mobilization and the activation of peroxisome proliferator-activated receptor gamma (PPARγ) nuclear receptor through the leukotriene B4 (LTB4) production. AA/LTB4/PPARγ/Dectin-1-MR signaling pathway is crucial for P17-mediated anti-fungal activity of h-MDMs, as indicated by the fact that the activation of this axis by P17 triggered ROS production and inflammasome-dependent IL-1β release. Moreover, we showed that the increased anti-fungal immune response of h-MDMs by P17 was dependent on intracellular calcium mobilization triggered by the interaction of P17 with pertussis toxin-sensitive G-protein-coupled receptors on h-MDMs. Finally, we also demonstrated that P17-treated mice infected with C. albicans develop less severe gastrointestinal infection related to a higher efficiency of their macrophages to engulf Candida, to produce ROS and IL-1β and to kill the yeasts. Altogether, these results identify P17 as an original activator of the fungicidal response of macrophages that acts upstream PPARγ/CLRs axis and offer new immunomodulatory therapeutic perspectives in the field of infectious diseases.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 78%

See 1 more Smart Citation

P17, an Original Host Defense Peptide from Ant Venom, Promotes Antifungal Activities of Macrophages through the Induction of C-Type Lectin Receptors Dependent on LTB4-Mediated PPARγ Activation

et al. 2017

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“…MALDI-TOF-TOF and de novo sequencing were used to assign the sequence of 28 peptides from 400 Da to 3900 Da in venom from the T. serrulatus, mostly as fragments of Pape proteins, corresponding to sequences from the N-terminal region of the TsKβ (scorpine-like) toxin, from potassium channel toxins (other than the k-beta ones), and from hypotensins [45,46]. Nascimento et al [43] investigated the general profile of polypeptide components from the venom of various scorpion species from 900 Da to 17.000 Da; the authors reported 632 components in T. stigmurus, 383 components in T. serrulatus, 464 components in T. bahiensis, 554 in Leiurus hebraeus, and 380 components in L.q.…”

Section: Introductionmentioning

confidence: 99%

Profiling the short, linear, non-disulfide bond-containing peptidome from the venom of the scorpion Tityus obscurus

Dias

Souza

Cocchi

et al. 2018

Journal of Proteomics

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The scorpion Tityus obscurus causes many envenoming accidents of medical importance in Brazilian Amazon region; despite to this, very few is known about the toxinology of this animal. The knowledge about the venom composition and mechanisms of action is very important to understand the physiopathology processes related to the envenoming caused by this animal. The proteopeptidomic investigations of scorpion venoms in general have focused mainly the neurotoxins (which are disulfide bonds containing peptides) and large proteins. The short, linear, non-disulfide bonds containing peptides (NDBPs) represent up to 5% of scorpion venom compositions; however, they have been few investigated in comparison with the neurotoxins. The present study used a mass spectrometric approach to detect 320 NDBPs and to sequence 27 of them; pharmacological assays permitted to characterize 13 NDBPs as novel toxins involved with inflammation, pain and edema formation.

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“…Recentemente, Pucca et al (2016c) demonstraram o efeito pró-inflamatório de três peptídeos derivados do veneno de Tityus serrulatus sobre uma linhagem de macrófagos murinos, com aumento da produção de IL-6. Como no nosso caso, os efeitos foram sutis quando comparados aos do LPS, apesar de significativos em relação ao controle negativo.…”

Section: Modulação Da Elastaseunclassified

Purificação e caracterização de peptídeos presentes no veneno do escorpião >i<Tityus serrulatus>/i<

Duzzi¹

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Non-disulfide-bridged peptides from Tityus serrulatus venom: Evidence for proline-free ACE-inhibitors

Cited by 14 publications

References 47 publications

P17, an Original Host Defense Peptide from Ant Venom, Promotes Antifungal Activities of Macrophages through the Induction of C-Type Lectin Receptors Dependent on LTB4-Mediated PPARγ Activation

P17, an Original Host Defense Peptide from Ant Venom, Promotes Antifungal Activities of Macrophages through the Induction of C-Type Lectin Receptors Dependent on LTB4-Mediated PPARγ Activation

Profiling the short, linear, non-disulfide bond-containing peptidome from the venom of the scorpion Tityus obscurus

Purificação e caracterização de peptídeos presentes no veneno do escorpião >i<Tityus serrulatus>/i<

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