Inhibition of prostaglandin synthesis after metabolism of menadione by cultured porcine endothelial cells

Journal Article · Sat Apr 01 04:00:00 EST 1989 · J. Clin. Invest.; (United States)

DOI:https://doi.org/10.1172/JCI113995· OSTI ID:6154395

Barchowsky, A; Tabrizi, K; Kent, R S; Whorton, A R

We have examined the effects of menadione on porcine aortic endothelial cell prostaglandin synthesis. Addition of 1-20 microM menadione caused a dose- and time-dependent inhibition of stimulated prostaglandin synthesis with an IC50 of 5 microM at 15 min. Concentrations greater than 100 microM menadione were necessary to increase /sup 51/Cr release from prelabeled cells. Recovery of enzyme inactivated by menadione required a 6-h incubation in 1% serum. In a microsomal preparation, menadione was shown to have no direct effect on conversion of arachidonic acid to prostaglandins. In intact cells menadione caused only a 40% inhibition of the conversion of PGH2 to prostacyclin. Enzymes involved in the incorporation and the release of arachidonic acid were not affected by menadione (20 microM, 15 min). Menadione undergoes oxidation/reduction reactions in intact cells leading to partial reduction of oxygen-forming, reactive oxygen species. In our cells menadione was found to increase KCN-resistant oxygen consumption. Further, an increased accumulation of H/sub 2/O/sub 2/ was observed with a time course consistent with menadione-induced inhibition of prostaglandin synthesis. We conclude that menadione at sublethal doses caused inhibition of prostaglandin synthesis. The mechanism involves inactivation of PGH2 synthase by a reactive species resulting from metabolism of menadione by endothelial cells.

• Research Organization: Duke Univ. Medical Center, Durham, NC (USA)
• OSTI ID: 6154395
• Journal Information: J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 83:4; ISSN JCINA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL TISSUES
ANIMALS
ARACHIDONIC ACID
AROMATICS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
BODY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL CULTURES
CHEMICAL REACTIONS
CHROMIUM 51
CHROMIUM ISOTOPES
COAGULANTS
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
ENDOTHELIUM
ENZYMES
EVEN-ODD NUCLEI
HEMATOLOGIC AGENTS
HEPARIN ANTAGONISTS
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
INHIBITION
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGASES
MAMMALS
METABOLISM
MICROSOMES
MONOCARBOXYLIC ACIDS
NONMETALS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
OXYGEN
OXYGEN COMPOUNDS
PEROXIDES
PROSTAGLANDINS
QUINONES
RADICALS
RADIOISOTOPES
REACTION KINETICS
REDOX REACTIONS
RUMINANTS
SHEEP
SWINE
SYNTHESIS
TIME DEPENDENCE
TISSUES
TRACER TECHNIQUES
VERTEBRATES
VITAMIN K
VITAMINS