Endogenous xanthine oxidase-derived O sub 2 metabolites inhibit surfactant metabolism

Journal Article · Mon Oct 01 00:00:00 EDT 1990 · American Journal of Physiology; (USA)

OSTI ID:6071940

Baker, R R; Panus, P C; Holm, B A; Engstrom, P C; Freeman, B A; Matalon, S ^[1]

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1. Univ. of Alabama, Birmingham (USA)

The ability of xanthine oxidase (XO)-derived, partially reduced O2 species (PROS) to inhibit surfactant production was examined in freshly isolated alveolar type II (ATII) pneumocytes from New Zealand White rabbits. (Methyl-3H)choline chloride and (1-14C)palmitate incorporation into phosphatidylcholine (PC) decreased in a dose-dependent manner, whereas peak media hydrogen peroxide (H2O2) concentration increased, when 1, 5, or 10 mU/ml XO were added to cell suspensions containing 500 microM xanthine. Addition of 100 microM allopurinol inhibited H2O2 production and abolished the decrease in choline and palmitate incorporation into PC. ATII cells incubated with 500 microM xanthine alone incorporated choline and palmitate at 90 and 80% of control levels, respectively. However, 100 microM allopurinol restored precursor incorporation to control values. To identify a possible intracellular source of PROS, ATII cell xanthine dehydrogenase (XDH) and XO activities were measured. Both total activity (XDH + XO; 45 +/- 7 microU/mg protein) and the percentage activity in the oxidase form (%XO; 30 +/- 4%) remained unchanged in ATII cells incubated in media only (control) for 2 h. In contrast, incubation of ATII cells with 500 microM xanthine resulted in a 50% loss of XDH + XO activity and a 21% increase in %XO within 10 min. After 2 h there was no measurable XDH + XO activity in xanthine-treated cells. Total XDH + XO activity in cells incubated with 500 microM xanthine and 100 microM allopurinol was less than 6% of control values throughout the incubation.

• OSTI ID: 6071940
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 259:4 Pt 1; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

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550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AROMATICS
AZAARENES
BIOCHEMICAL REACTION KINETICS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
DOSE-RESPONSE RELATIONSHIPS
ENZYME ACTIVITY
ENZYMES
HETEROCYCLIC COMPOUNDS
HEXADECANOIC ACID
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
KINETICS
LABELLED COMPOUNDS
LUNGS
MAMMALS
METABOLISM
METABOLITES
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEROXIDES
PURINES
RABBITS
REACTION KINETICS
RESPIRATORY SYSTEM
SURFACTANTS
TRITIUM COMPOUNDS
VERTEBRATES
XANTHINES