Effect of variable glutathione peroxidase activity on H/sub 2/O/sub 2/-related cytotoxicity in cultured aortic endothelial cells
Primary cultures of porcine aortic endothelial cells were used to assess the effects of O/sub 2/ intermediates produced by 10-40 mU/ml xanthine oxidase (XO; +2 mM hypoxanthine) or 25-100 mU/ml glucose oxidase (GO; +5 mM glucose). A 60-min incubation in the presence of the enzyme systems resulted in a dose-dependent toxic effect with evidence of cytolysis (increased LDH release) and cell loss (decrease in DNA and protein content), when these indexes were measured 24 hr after completion of the enzyme reaction. Decreased (/sup 3/H)thymidine incorporation into DNA was the most sensitive index of cell dysfunction for both enzyme systems. The effects of various scavengers and enzymes indicated that H/sub 2/O/sub 2/ was the main O/sub 2/ intermediate involved in the cytotoxicity resulting from the XO-hypoxanthine reaction. Increased glutathione peroxidase activity associated with the addition of 2 x 10/sup -7/ M selenomethionine to culture medium had a partial protective effect which could be related to an increased rate of H/sub 2/O/sub 2/ degradation. Evidence for increased DNA synthesis after injury was found in cells previously exposed to XO-hypoxanthine, the degree of increase in (/sup 3/H)thymidine incorporation being dependent on the intensity of the initial cytotoxicity.
- Research Organization:
- Hospital Cantonal Universitaire, Geneva, Switzerland
- OSTI ID:
- 6376454
- Journal Information:
- Proc. Soc. Exp. Biol. Med.; (United States), Vol. 180:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HYDROGEN PEROXIDE
TOXICITY
METHIONINE
BIOLOGICAL EFFECTS
OXIDOREDUCTASES
ENZYME ACTIVITY
SELENIUM COMPOUNDS
ANIMAL CELLS
AORTA
CELL CULTURES
DNA
DNA REPLICATION
DOSE-RESPONSE RELATIONSHIPS
ENDOTHELIUM
GLUTATHIONE
HYPOXANTHINE
RESPONSE MODIFYING FACTORS
SWINE
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINO ACIDS
ANIMAL TISSUES
ANIMALS
AROMATICS
ARTERIES
AZAARENES
AZINES
BLOOD VESSELS
BODY
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
DOMESTIC ANIMALS
DRUGS
ENZYMES
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPOTROPIC FACTORS
MAMMALS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PEPTIDES
PEROXIDES
POLYPEPTIDES
PROTEINS
PURINES
PYRIMIDINES
RADIOPROTECTIVE SUBSTANCES
RIBOSIDES
TISSUES
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)