title: The natural stilbenoid piceatannol decreases activity and accelerates apoptosis of human neutrophils: involvement of protein kinase C.
abstract: Neutrophils are able to release cytotoxic substances and inflammatory mediators, which, along with their delayed apoptosis, have a potential to maintain permanent inflammation. Therefore, treatment of diseases associated with chronic inflammation should be focused on neutrophils; formation of reactive oxygen species and apoptosis of these cells represent two promising targets for pharmacological intervention. Piceatannol, a naturally occurring stilbenoid, has the ability to reduce the toxic action of neutrophils. This substance decreased the amount of oxidants produced by neutrophils both extra- and intracellularly. Radicals formed within neutrophils (fulfilling a regulatory role) were reduced to a lesser extent than extracellular oxidants, potentially dangerous for host tissues. Moreover, piceatannol did not affect the phosphorylation of p40(phox)-a component of NADPH oxidase, responsible for the assembly of functional oxidase in intracellular (granular) membranes. The stilbenoid tested elevated the percentage of early apoptotic neutrophils, inhibited the activity of protein kinase C (PKC)-the main regulatory enzyme in neutrophils, and reduced phosphorylation of PKC isoforms α , β II, and δ on their catalytic region. The results indicated that piceatannol may be useful as a complementary medicine in states associated with persisting neutrophil activation and with oxidative damage of tissues.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratislava, Slovakia.
authors.forename: Viera
authors.initials: V
authors.lastname: Jancinova
authors.forename: Tomas
authors.initials: T
authors.lastname: Perecko
authors.forename: Radomir
authors.initials: R
authors.lastname: Nosal
authors.forename: Klara
authors.initials: K
authors.lastname: Svitekova
authors.forename: Katarina
authors.initials: K
authors.lastname: Drabikova
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D002469:Cell Separation; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001688:Biological Products; D010750:Phosphoproteins; D013267:Stilbenes; C085072:neutrophil cytosol factor 40K; C041525:3,3',4,5'-tetrahydroxystilbene; D011493:Protein Kinase C