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A Simplified and Efficient Method to Isolate Primary Human Keratinocytes from Adult Skin Tissue
Published on: August 25, 2018
VIP-derived sequences modified by N-terminal stearyl moiety induce cell death: the human keratinocyte as a model
R Granoth1, M Fridkin, S Rubinraut
1Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Abstract:
Vasoactive intestinal peptide (VIP) is a recognized growth factor affecting many cell types. We have previously developed a series of lipophilic VIP analogues containing an N-terminal covalently attached stearyl moiety. The current studies identified stearyl-Nle(17)-VIP and stearyl-Nle(17)-neurotensin(6-11)VIP(7-28), acting at microM concentrations, as cytotoxic to human keratinocytes. The core C-terminal active VIP-derived peptide, stearyl-Lys-Lys-Tyr-Leu-NH(2) (St-KKYL-NH(2)), was identified as being responsible for the observed cytotoxicity. Cytotoxicity coincided with marked reduction in intracellular cyclic GMP and was abolished by co-treatment with the endonuclease inhibitor, aurine-tricarboxylic acid, suggesting apoptotic mechanisms. Stearyl-VIP derivatives thus offer lead compounds for future drug development against hyperproliferative skin conditions.
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