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Modulation of prostaglandin H synthase activity by conjugated linoleic acid (CLA) and specific CLA isomers
Author(s) -
Bulgarella Jennifer A.,
Patton David,
Bull Arthur W.
Publication year - 2001
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-001-0736-2
Subject(s) - conjugated linoleic acid , chemistry , arachidonic acid , microsome , enzyme , prostaglandin , linoleic acid , clinical chemistry , stereochemistry , biochemistry , fatty acid
Conjugated linoleic acid (CLA) has been shown to inhibit tumorigenesis in animal models and is cytostatic to numerous cell lines in vitro . However, the mechanism of action is unknown. In the current study, we determined the effects of CLA and specific isomers of CLA on the rate of oxygenation of arachidonic acid by prostaglandin H synthase (PGHS) in ram seminal vesicle microsomes. The enzyme was incubated with 0.1 to 100 μM CLA or specific isomers of CLA for 2 min prior to the addition of 44 to 176 μM arachidonate. The isomers tested were 9( E ),11( E ) CLA; 9( Z ),11( E ) CLA; 9( Z ),11( Z ) CLA, and 10( E ),12( Z ) CLA. For a positive inhibitor control, flurbiprofen was used at 0.75 to 2.50 μM. Enzyme activity was assessed by measuring the rate of oxygen consumption. Inclusion of CLA or specific isomers of CLA in the incubation mixtures inhibits PGHS. The efficacy differs for each isomer, with the 9( Z ),11( E ) CLA isomer being the most effective and the 9( Z ),11( Z ) CLA isomer being the least effective inhibitor among the four CLA isomers tested. The K i values obtained by Dixon replots range from 18.7 μM for the most effective isomer, 9( Z ),11( Z ) CLA, to 105.3 μM for the least effective isomer, 9( Z ),11( Z ) CLA. The K i value for flurbiprofen with ram seminal vesicle microsomes was 0.33 μM. As the concentration of arachidonate was increased, the CLA‐dependent inhibition of PGHS decreased, suggesting competitive inhibition. The results of this study demonstrate the potential of CLA and specific isomers of CLA to modulate prostaglandin biosynthesis.