Recovery of prostacyclin synthesis in vascular smooth muscle cells following self-inactivation and requirement for growth factors
The cyclooxygenase enzyme system is a prime example of a metabolic pathway that is regulated by self inactivation. This is believed to occur in part via the irreversible reaction of the endoperoxide intermediate species with the cyclooxygenase enzyme. This inactivation and recovery of activity is similar to the inactivation observed with aspirin which irreversibly acetylates the enzyme. Self inactivation was studied in cultured rat and bovine aorta smooth muscle cells. The production of the prostanoid PGI2 was demonstrated by incubation of a monolayer of cells with 12 ..mu..M C-14 labeled arachidonic acid. Products were analyzed by thin layer chromatography and identified by their comigration with authentic standards and confirmed by gas chromatography/mass spectrometry. Preincubation of the cells for 10 minutes with arachidonic acid at concentrations as low as 1 ..mu..g/mL inactivated the cells to a second challenge with radiolabeled arachidonic acid. Recovery from self inactivation took place over a three hour time period and was similar to the recovery observed with aspirin pretreatment. Recovery was inhibited by addition of 10 ..mu..g/mL cycloheximide to the medium indicating that it involves synthesis of cyclooxygenase protein. Epidermal growth factor was identified as a serum factor responsible for the rapid recovery of cyclooxygenase activity in rat and bovine aorta smooth muscle cells.
- Research Organization:
- George Washington Univ. of School of Medicine and Health Sciences, Washington, DC
- OSTI ID:
- 7025291
- Report Number(s):
- CONF-8606151-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
Similar Records
Arachidonate metabolism in bovine gallbladder muscle
Ozone-induced alterations in arachidonic acid metabolism in cultured lung cell types
Related Subjects
HORMONES
BIOCHEMICAL REACTION KINETICS
OXYGENASES
ENZYME ACTIVITY
PROSTAGLANDINS
BIOSYNTHESIS
AORTA
ARACHIDONIC ACID
BIOLOGICAL PATHWAYS
CARBON 14 COMPOUNDS
CATTLE
GAS CHROMATOGRAPHY
INACTIVATION
MASS SPECTROSCOPY
METABOLISM
MUSCLES
RATS
SALICYLIC ACID
THIN-LAYER CHROMATOGRAPHY
TRACER TECHNIQUES
ANIMALS
ARTERIES
BLOOD VESSELS
BODY
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
CHROMATOGRAPHY
DOMESTIC ANIMALS
ENZYMES
HYDROXY ACIDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
REACTION KINETICS
RODENTS
RUMINANTS
SEPARATION PROCESSES
SPECTROSCOPY
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques