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Development of novel cellular model for affinity studies of histamine H4 receptor ligands

100%
Karcz T., Kieć-Kononowicz K.
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2013
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vol. 60
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issue 4
823-827
EN
The G protein-coupled histamine H4 receptor (H4R) is the last member of histamine receptors family discovered so far. Its expression pattern, together with postulated involvement in a wide variety of immunological and inflammatory processes make histamine H4 receptor an interesting target for drug development. Potential H4R ligands may provide an innovative therapies for different immuno-based diseases, including allergy, asthma, pruritus associated with allergy or autoimmune skin conditions, rheumatoid arthritis and pain. However, none of successfully developed selective and potent histamine H4 receptor ligands have been introduced to the market up to date. For that reason there is still a strong demand for pharmacological models to be used in studies on potent H4R ligands. In current work we present the development of novel mammalian cell line, stably expressing human histamine H4 receptor, with use of retroviral transduction approach. Obtained cell line was pharmacologically characterized in radioligand binding studies and its utility for affinity testing of potent receptor ligands was confirmed in comparative studies with the use of relevant insect cells expression model. Obtained results allow for statement that developed cellular model may be successfully employed in search for new compounds active at histamine H4 receptor.
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The study of cellular cytotoxicity of argireline® - an anti-aging peptide

71%
Grosicki M., Latacz G., Szopa A., Cukier A., Kieć-Kononowicz K.
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2014
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vol. 61
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issue 1
29-32
EN
Argireline® is well know, innovative anti-aging product used in the cosmetic market. This short chain peptide is used as active ingredient in dermal ointment and creams. Argireline® prevents formation of skin lines and wrinkles in a very similar way to the botulinum toxin (Botox), inhibiting neurotransmitter release at the neuromuscular junction. Argireline® does not require under skin muscle injections and it is believed to be relatively safe. However, despite the fact that some toxicity data has been provided by the product manufacturer, there is an evident lack of reliable information about cytotoxicity of argireline® in the literature. The aim of the presented study was to estimate the antiproliferation effect of argireline® solution in several concentrations. The influence of argireline® on cellular proliferation was examined against: human embryonic kidney HEK-293 cell line, human neuroblastoma IMR-32 cell line, and human primary skin fibroblasts. Tests were performed using formazan-based cell proliferation assay: EZ4U, which allows to measure the efficiency of mitochondrial oxidative activity in living cells. The argireline® inhibitory concentration, IC50 values were calculated and the results were compared to the IC50 value of the reference compound: doxorubicin. In conclusion, the considered method resulted in dose-dependent argireline® anti-proliferation effects. However, the significant cytotoxicity of argireline® solution was observed under 18 to 10 000 fold higher concentrations (depending on cells that were examined) in comparison to doxorubicin.
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