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Hydrolysis of inositol phospholipids precedes cellular proliferation in asbestos-stimulated tracheobronchial epithelial cells

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America; (USA)
;  [1];  [2]
  1. Univ. of Vermont College of Medicine, Burlington (USA)
  2. W. Alton Jones Cell Science Center, Lake Placid, NY (USA)

Metabolism of inositol phospholipids and phosphatidylcholine was investigated in tracheobronchial epithelial cells exposed to mitogenic concentrations of crocidolite asbestos. Alterations in levels of diacylglycerol, the endogenous activator of protein kinase C, and inositol polyphosphates, presumed mobilizers of intracellular calcium, were examined. Cultures labeled with ({sup 3}H)diacylglycerol. In contrast, crocidolite-exposed cells labeled with ({sup 3}H)myristic acid or ({sup 3}H)choline did not display elevated production of ({sup 3}H)diacylglycerol or release of ({sup 3}H)choline metabolites (i.e., evidence of phosphatidylcholine hydrolysis). The soluble tumor promoter phorbol 12-myristate 13-acetate catalyzed both of these changes. myo-({sup 3}H)Inositol-labeled cells exposed as briefly as 10 min to mitogenic concentrations of crocidolite demonstrated elevations in ({sup 3}H)inositol mono-, tris-, and terakisphosphates, phenomena indicating turnover of inositol phospholipids. The detection of diacylglycerol and inositol phosphates in crocidolite asbestos-exposed cells suggests that this fibrous tumor promoter activates phospholipase C as it stimulates cellular proliferation.

OSTI ID:
5682009
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:19; ISSN 0027-8424; ISSN PNASA
Country of Publication:
United States
Language:
English