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

Our plain-English summary of Hydrolysis of inositol phospholipids precedes cellular proliferation in asbestos-stimulated tracheobronchial epithelial cells, by A. Sesko, M. Cabot, B. Mossman (Proceedings of the National Academy of Sciences of the United States of America, 1990).

The study

• Authors: A. Sesko, M. Cabot, B. Mossman
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Published: 1990;87(19):7385-9
• Cited by: 35 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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 [3H]glycerol and exposed to proliferative concentrations of crocidolite asbestos demonstrated significant elevations in [3H]diacylglycerol. In contrast, crocidolite-exposed cells labeled with [3H]myristic acid or [3H]choline did not display elevated production of [3H]diacylglycerol or release of [3H]choline metabolites--i.e., evidence of phosphatidylcholine hydrolysis. The soluble tumor promoter phorbol 12-myristate 13-acetate catalyzed both of these changes. myo-[3H]Inositol-labeled cells exposed as briefly as 10 min to mitogenic concentrations of crocidolite demonstrated elevations in [3H]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.

In plain English

This was a laboratory study of cultured cells, not of people. The authors exposed hamster tracheal epithelial (HTE) cells to crocidolite asbestos. The cells were cloned from the airway lining of a newborn female golden Syrian hamster. The authors used crocidolite concentrations they described as growth-stimulatory and measured breakdown products of fat molecules in the cells. Nonfibrous riebeckite and glass beads were used as comparison particles. After 120 minutes, crocidolite at 0.1 micrograms per square centimeter of dish lowered labeled phospholipids and raised diacylglycerol, a natural activator of the enzyme protein kinase C. In that experiment, other crocidolite concentrations did not raise diacylglycerol. Unlike the chemical tumor promoter PMA, crocidolite did not cause breakdown of phosphatidylcholine. Crocidolite at 0.1 micrograms per square centimeter raised inositol tetrakisphosphate at 10, 30 and 60 minutes and inositol trisphosphate at 10 minutes. Riebeckite and glass beads, at 0.1 to 5 micrograms per square centimeter for 120 minutes, caused no detectable changes in phospholipid metabolites. The authors concluded that these findings strongly suggest the fibers activate an enzyme called phospholipase C. They noted variability in their measurements.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell culture experiment
• Who was studied: Hamster tracheal epithelial (HTE) cells cloned from the tracheobronchial epithelium of a female neonatal golden Syrian hamster. Groups were generally 3 or 4 dishes, and experiments were repeated two to three times.
• Exposure: Union Internationale Contre le Cancer reference crocidolite asbestos at concentrations from 0.05 to 5 micrograms per square centimeter of dish, for 10 to 240 minutes. Riebeckite (nonfibrous) and glass beads were negative controls. Phospholipase C, PMA and bombesin were comparison agents.
• Main results:
  • In glycerol-labeled cells after 120 minutes, crocidolite at 0.1 micrograms per square centimeter decreased radiolabeled phospholipids and increased radiolabeled diacylglycerol (acyl2Gro). In that experiment, other asbestos concentrations did not increase acyl2Gro.
  • In Table 1 at 120 minutes, radiolabeled acyl2Gro was 603 plus or minus 36 in controls, 1,682 plus or minus 120 with phospholipase C, and 1430 plus or minus 127 with crocidolite at 0.1 micrograms per square centimeter (mean plus or minus SEM, n = 3 plates per group).
  • Crocidolite did not induce phosphatidylcholine turnover. Myristate-labeled cells showed no rise in acyl2Gro, and crocidolite-exposed cultures did not differ from untreated controls in choline metabolite release. PMA at 100 ng/ml did release choline metabolites from 30 minutes onward.
  • Crocidolite at 0.1 micrograms per square centimeter significantly increased inositol tetrakisphosphate at 10, 30 and 60 minutes, and inositol trisphosphate at 10 minutes.
  • Crocidolite at 0.5 micrograms per square centimeter, described as neither stimulatory nor cytotoxic, gave inositol phosphate levels approximating those of untreated controls.
  • Riebeckite and glass beads at 0.1 to 5 micrograms per square centimeter for 120 minutes caused no detectable changes in phospholipid metabolites.
• The authors' conclusion: The authors concluded that detecting diacylglycerol and inositol phosphates in asbestos-exposed cells strongly suggests that phospholipase C is activated in response to the fibers.
• Limitations the authors state:
  • The authors noted variability in the measurements, shown by inconsistent phospholipid reductions with phospholipase C over time.
  • For reductions in phospholipid radioactivity, statistical analysis could distinguish only the 0.1 microgram per square centimeter concentration from the untreated control.
  • A second separation method failed to reveal which phospholipid the diacylglycerol came from.
  • The authors said other explanations for the delayed accumulation of diacylglycerol cannot be ruled out.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Crocidolite.

Related studies

• Effects of crocidolite and chrysotile asbestos on cellular uptake and metabolism of benzo(a)pyrene in hamster tracheal epithelial cells — B.T. Mossman, A. Eastman, et al. (1983)
• Transfection of a manganese-containing superoxide dismutase gene into hamster tracheal epithelial cells ameliorates asbestos-mediated cytotoxicity — B.T. Mossman, P. Surinrut, et al. (1996)
• Mechanisms of asbestos-induced squamous metaplasia in tracheobronchial epithelial cells — G. Cameron, C.D. Woodworth, et al. (1989)
• Ozone enhances the uptake of mineral particles by tracheobronchial epithelial cells in organ culture — A. Churg, M. Brauer, et al. (1996)
• Asbestos induces nuclear factor kappa B (NF-kappa B) DNA-binding activity and NF-kappa B-dependent gene expression in tracheal epithelial cells — Y.M. Janssen, A. Barchowsky, et al. (1995)
• Mineralogical features associated with cytotoxic and proliferative effects of fibrous talc and asbestos on rodent tracheal epithelial and pleural mesothelial cells — A.G. Wylie, H.C. Skinner, et al. (1997)

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