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

Conlon, JM, Musale, V, Attoub, S, Mangoni, ML, Leprince, J, Coquet, L, Jouenne, T, Abdel-Wahab, YHA, Flatt, Peter and Rinaldi, AC (2017) Cytotoxic peptides with insulin-releasing activities from skin secretions of the Italian stream frog Rana italica (Ranidae). Journal of Peptide Science, 23 (10). pp. 769-776. [Journal article]

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DOI: 10.1002/psc.3025

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.

Item Type:Journal article
Keywords:Frog skin; Antimicrobial peptide; Cytotoxicity; Ranidae, Insulin release
Faculties and Schools:Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:38363
Deposited By: Dr Nigel Irwin
Deposited On:18 Jul 2017 08:33
Last Modified:12 Jul 2018 22:23

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