Cytotoxic peptides with insulin-releasing activities from skin secretions of the Italian stream frog Rana italica (Ranidae)

J. Michael Conlon, Vishal Musale, Samir Attoub, Maria Luisa Mangoni, Jérôme Leprince, Laurent Coquet, Thierry Jouenne, Yasser H.A. Abdel-Wahab, Peter R. Flatt, Andrea C. Rinaldi

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Peptidomic analysis of norepinephrine-stimulated skin secretions from Italian stream frog Rana italica led to the purification and characterization of two host-defense peptides differing by a single amino acid residue belonging to the brevinin-1 family (brevinin-1ITa and -1ITb), a peptide belonging to the temporin family (temporin-ITa) and a component identified as prokineticin Bv8. The secretions contained relatively high concentrations of the methionine-sulphoxide forms of brevinin-1ITa and -1ITb suggesting that these peptides may have a role as antioxidants in the skin of this montane frog. Brevinin-1ITa (IVPFLLGMVPKLVCLITKKC) displayed potent cytotoxicity against non-small cell lung adenocarcinoma A549 cells (LC50 = 18 μM), breast adenocarcinoma MDA-MB-231 cells (LC50 = 8 μM) and colorectal adenocarcinoma HT-29 cells (LC50 = 18 μM), but the peptide was also strongly hemolytic against mouse erythrocytes (LC50 = 7 μM). Temporin-ITa (VFLGAIAQALTSLLGKL.NH2) was between three and fivefold less potent against these cells. Brevinin-1ITa inhibited growth of both Gram-positive Staphylococcus epidermidis and Gram-negative Escherichia coli as well as a strain of the opportunist yeast pathogen Candida parapsilosis, whereas temporin-ITa was active only against S. epidermidis and C. parapsilosis. Both peptides stimulated the release of insulin from BRIN-BD11 clonal β-cells at concentrations ≥1 nM, but brevinin-1ITa was cytotoxic to the cells at concentrations ≥3 μM.

Original languageEnglish
Pages (from-to)769-776
Number of pages8
JournalJournal of Peptide Science
Volume23
Issue number10
DOIs
Publication statusPublished - Oct 2017

Keywords

  • Ranidae
  • antimicrobial peptide
  • cytotoxicity
  • frog skin
  • insulin release

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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