Study of Possible Mechanisms Involved in the Inhibitory Effects of Coumarin Derivatives on Neutrophil Activity

0421993 - ÚOCHB 2014 RIV US eng J - Journal Article
Drábiková, K. - Perečko, T. - Nosáľ, R. - Harmatha, Juraj - Šmidrkal, J. - Jančinová, V.
Study of Possible Mechanisms Involved in the Inhibitory Effects of Coumarin Derivatives on Neutrophil Activity.
Oxidative Medicine and Cellular Longevity. Roč. 2013, October (2013), 136570/1-136570/10. ISSN 1942-0900. E-ISSN 1942-0994
Institutional support: RVO:61388963
Keywords : protein-kinase-C * phagocyte NADPH oxidase * antioxidant activity
Subject RIV: CC - Organic Chemistry
Impact factor: 3.363, year: 2013
http://www.hindawi.com/journals/omcl/2013/136570/

To specify the site of action of the synthetic coumarin derivatives 7-hydroxy-3-(4'-hydroxyphenyl) coumarin (HHC) and 7-hydroxy-3-(4'-hydroxyphenyl) dihydrocoumarin (HHDC), we evaluated their effects on extra-and intracellular reactive oxygen species (ROS) formation in phorbol-myristate-13-acetate (PMA) stimulated human neutrophils. We studied also the effects of HHC and HHDC on possible molecular mechanisms which participate in the activation of NADPH oxidase, that is, on PKC activity, on phosphorylation of some PKC isoforms (alpha, beta II, and delta), and on phosphorylation of the NADPH oxidase subunit p40(phox). Without affecting cytotoxicity, both coumarines tested were effective inhibitors/scavengers of ROS produced by neutrophils on extracellular level. HHC markedly diminished oxidant production and also, intracellularly, decreased PKC activity and partly phosphorylation of PKC alpha, beta II. On the other hand, we did not observe any effect of coumarin derivatives on phosphorylation of PKC delta and on phosphorylation of the NADPH oxidase subunit p40(phox), which were suggested to be involved in the PMA-dependent intracellular activation process. In agreement with our previous findings, we assume that the different molecular structures of HHC and HHDC with their different physicochemical and free radical scavenging characteristics are responsible for their diverse effects on the parameters tested.
Permanent Link: http://hdl.handle.net/11104/0228275