Regulation of cyclooxygenase expression in cultured vascular cells
Arachidonic acid metabolism in vascular tissue results in synthesis of prostacylin. The key enzyme in this synthesis pathway, cyclooxygenase, is down-regulated through self-inactivation. An analogous refractory state is produced by aspirin which irreversibly acetylates the enzyme. To further understand this phenomenon, the inactivation and recovery of cyclooxygenase activity was assayed in cultured ray vascular smooth muscle cells using exogenously added arachidonic acid. Self-inactivation of cyclooxygenase was observed following treatment with micromolar amounts of arachidonic acid. The recovery of cyclooxygenase activity following self-inactivation was analogous to that observed following aspirin-inactivation in that it depended on protein synthesis and required either serum or EGF. Two additional factors, TGF-{beta} and uric acid, were found to enhance the stimulation of cyclooxygenase recovery by EGF. A defined medium containing 10 ng/mL EGF, 1 ng/mL TGF{beta} and 0.1 mM uric acid duplicated the cyclooxygenase recovery activity of 10% serum. Stimulation of cyclooxygenase activity by EGF and TGF-{beta} was inhibited by cycloheximide but not by actinomycin-D, indicating a link to increased translation of pre-existing mRNA. A lack of significant effect on overall protein synthesis by EGF and TGF-{beta}, measured by ({sup 35}S)-methionine incorporation under conditions where a multi-fold increase in cyclooxygenase activity was seen, indicates that the translational regulation of a small fraction of total mRNA and possibly cyclooxygenase is occurring.
- Research Organization:
- George Washington Univ., Washington, DC (USA)
- OSTI ID:
- 5600762
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ARACHIDONIC ACID
METABOLISM
GROWTH FACTORS
BIOCHEMICAL REACTION KINETICS
OXYGENASES
ENZYME ACTIVITY
PROSTAGLANDINS
BIOSYNTHESIS
SALICYLIC ACID
BIOLOGICAL PATHWAYS
BLOOD VESSELS
CELL CULTURES
MESSENGER-RNA
METHIONINE
MUSCLES
SULFUR 35
TRACER TECHNIQUES
AMINO ACIDS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
DAYS LIVING RADIOISOTOPES
DRUGS
ENZYMES
EVEN-ODD NUCLEI
HYDROXY ACIDS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
LIPOTROPIC FACTORS
MITOGENS
MONOCARBOXYLIC ACIDS
NUCLEI
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OXIDOREDUCTASES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RNA
SULFUR ISOTOPES
SYNTHESIS
550201* - Biochemistry- Tracer Techniques
550501 - Metabolism- Tracer Techniques