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Title: Effects of dexamethasone on palate mesenchymal cell phospholipase activity

Corticosteroids will induce cleft palate in mice. One suggested mechanism for this effect is through inhibition of phospholipase activity. This hypothesis was tested by measuring the effects of dexamethasone, a synthetic corticosteroid, on phospholipase activity in cultures of palate mesenchymal cells. Palate mesenchymal cells were prelabeled with (3H)arachidonic acid. The cells were subsequently treated with various concentrations of dexamethasone. Concurrently, cultures of M-MSV-transformed 3T3 cells were prepared identically. After treatment, phospholipase activity was stimulated by the addition of serum or epidermal growth factor (EGF), and radioactivity released into the medium was taken as a measure of phospholipase activity. Dexamethasone (1 X 10(-5) or 1 X 10(-4) M) could inhibit serum-stimulated phospholipase activity in transformed 3T3 cells after 1 to 24 hr of treatment. However, no inhibition of activity was measured in palate mesenchymal cells following this period of treatment. Not until 120 hr of treatment with dexamethasone (1 X 10(-4) M) was any significant inhibition of serum-stimulated phospholipase activity observed in palate mesenchymal cells. When EGF was used to stimulate phospholipase activity, dexamethasone (1 X 10(-5) M) caused an increase in phospholipase activity in palate mesenchymal cells. These observations suggested that phospholipase in transformed 3T3 cells was sensitive to inhibitionmore » by dexamethasone. However, palate mesenchymal cell phospholipase is only minimally sensitive to dexamethasone, and in certain instances can be enhanced. These results cannot support the hypothesis that corticosteroids mediate their teratogenic effect via inhibition of phospholipase activity.« less
Authors:
;
Publication Date:
OSTI Identifier:
6304724
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicol. Appl. Pharmacol.; (United States); Journal Volume: 75:2
Research Org:
Children's Hospital Research Foundation, Cincinnati, OH
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; DEXAMETHASONE; BIOLOGICAL EFFECTS; PHOSPHOHYDROLASES; ENZYME ACTIVITY; CELL CULTURES; CONGENITAL MALFORMATIONS; ORAL CAVITY; SOMATIC CELLS; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ACID ANHYDRASES; ADRENAL HORMONES; ANIMAL CELLS; CORTICOSTEROIDS; DIGESTIVE SYSTEM; ENZYMES; GLUCOCORTICOIDS; HORMONES; HYDROLASES; HYDROXY COMPOUNDS; ISOTOPE APPLICATIONS; KETONES; LABELLED COMPOUNDS; MALFORMATIONS; ORGANIC COMPOUNDS; PATHOLOGICAL CHANGES; PREGNANES; STEROID HORMONES; STEROIDS 550201* -- Biochemistry-- Tracer Techniques