Adenine nucleotide depletion from endothelial cells exposed to xanthine oxidase

Journal Article · Sat Dec 01 04:00:00 EST 1990 · American Journal of Physiology; (USA)

OSTI ID:6249202

Aalto, T K; Raivio, K O ^[1]

---

1. Univ. of Helsinki (Finland)

Hypoxia causes breakdown of cellular nucleotides, accumulation of hypoxanthine (HX), and conversion of xanthine dehydrogenase into xanthine oxidase (XO). Upon reoxygenation, the HX-XO reaction generates free radicals, one potential mechanism of tissue damage. Because endothelial cells contain XO and are exposed to circulating HX, they are a likely target for damage. We studied the effect of XO and/or HX at physiologically relevant concentrations on nucleotide metabolism of cultured endothelial cells from human umbilical veins. Cells were labeled with (14C)adenine and incubated for up to 6 h with HX, XO, or both, in the absence or presence of serum. Adenine nucleotides from cell extracts and nucleotide breakdown products (HX, xanthine, and urate) from the medium were separated and counted. HX alone had no effect. XO (80 mU/ml) alone caused a 70% (no serum) or 40% (with serum) fall in adenine nucleotides and an equivalent increase of xanthine and urate. The combination of HX and XO caused a 90% (no serum) or 70% (with serum) decrease in nucleotides, decrease in energy charge, and detachment of cells from the culture plate. Nucleotide depletion was not accounted for by proteolytic activity in the XO preparation. Albumin was only half as effective as serum in preventing nucleotide loss. Thus exogenous XO, in the presence of endogenous HX, triggers adenine nucleotide catabolism, but endogenous XO activity is too low to influence nucleotide levels even at high exogenous HX concentrations. Serum limits the catabolic effect of XO and thus protects cells from free radical damage.

• OSTI ID: 6249202
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 259:6 Pt 1; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENINES
AMINES
ANIMAL TISSUES
ANIMALS
ANOXIA
ANTIMETABOLITES
AROMATICS
AZAARENES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL ACCUMULATION
BODY
CARBON 14 COMPOUNDS
CATABOLISM
DRUGS
ENDOTHELIUM
ENZYMES
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
HYPOXANTHINE
ISOTOPE APPLICATIONS
ISOTOPE DILUTION
KINETICS
LABELLED COMPOUNDS
MAMMALS
MAN
METABOLISM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
PRIMATES
PURINES
RADICALS
REACTION KINETICS
TISSUES
TRACER TECHNIQUES
VERTEBRATES