TY - JOUR
T1 - VIP-derived sequences modified by N-terminal stearyl moiety induce cell death
T2 - The human keratinocyte as a model
AU - Granoth, Ruth
AU - Fridkin, Mati
AU - Rubinraut, Sara
AU - Gozes, Illana
PY - 2000/6/16
Y1 - 2000/6/16
N2 - 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-Nle17-VIP and stearyl-Nle17-neurotensin6-11VIP7-28, acting at μM concentrations, as cytotoxic to human keratinocytes. The core C-terminal active VIP-derived peptide, stearyl-Lys-Lys-Tyr-Leu-NH2 (St-KKYL-NH2), 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. Copyright (C) 2000 Federation of European Biochemical Societies.
AB - 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-Nle17-VIP and stearyl-Nle17-neurotensin6-11VIP7-28, acting at μM concentrations, as cytotoxic to human keratinocytes. The core C-terminal active VIP-derived peptide, stearyl-Lys-Lys-Tyr-Leu-NH2 (St-KKYL-NH2), 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. Copyright (C) 2000 Federation of European Biochemical Societies.
KW - Aurine-tricarboxylic acid
KW - Keratinocyte cytotoxicity
KW - Lipophilic peptide
KW - Vasoactive intestinal peptide
KW - cGMP
UR - http://www.scopus.com/inward/record.url?scp=0034674642&partnerID=8YFLogxK
U2 - 10.1016/S0014-5793(00)01629-X
DO - 10.1016/S0014-5793(00)01629-X
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AN - SCOPUS:0034674642
VL - 475
SP - 71
EP - 77
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 2
ER -