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Related Experiment Videos

Dexamethasone-induced decrease in HMG-CoA reductase and protein-farnesyl transferase activities does not impair ras

M Lambert1, N D Bui

  • 1Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Brussels, Belgium.

Molecular and Cellular Biochemistry
|March 8, 2000
PubMed
Summary

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Dexamethasone induces differentiation in rat pancreatic cells by altering isoprenoid synthesis. Despite decreased farnesyl transferase activity, ras proteins remained functional, suggesting precursor availability was not limiting.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Rat pancreatic acinar cells (AR 4-2J) differentiate and reduce proliferation when treated with dexamethasone.
  • Isoprenoid synthesis, involving farnesyl and geranylgeranyl groups, is crucial for protein function, including ras proteins involved in cell regulation.

Purpose of the Study:

  • To investigate the effects of dexamethasone on the mevalonate pathway and farnesyl transferase activity in AR 4-2J cells.
  • To determine if changes in isoprenoid precursor levels or enzyme activity limit ras protein farnesylation and function.

Main Methods:

  • AR 4-2J cells were treated with dexamethasone.
  • Protein labeling with [3H]-mevalonolactone was used to assess isoprenoid synthesis.
  • HMG-CoA reductase activity and farnesyl transferase activity were measured.

Related Experiment Videos

  • Levels of isoprenylated ras proteins were analyzed.

    • Main Results:

    • Dexamethasone treatment increased protein labeling with [3H]-mevalonolactone.
    • HMG-CoA reductase activity decreased, reducing isotopic dilution of the mevalonate precursor.
    • Farnesyl transferase activity showed a dose-dependent decrease in dexamethasone-treated cells.
    • No non-isoprenylated ras proteins were observed, even with reduced enzyme activity.

    Conclusions:

    • Dexamethasone impacts the mevalonate pathway and farnesyl transferase activity in rat pancreatic acinar cells.
    • Despite observed decreases, isoprenoid precursor levels and farnesyl transferase activity were sufficient to maintain ras protein farnesylation in this model.