Glucose regulates protein catabolism in ras-transformed fibroblasts through a lysosomal-dependent proteolytic pathway

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C Tournu1, A Obled, M P Roux

  • 1UR 238, Unité de Nutrition Cellulaire et Moléculaire, Centre de Recherche en Nutrition Humaine, Institut National de la Recherche Agronomique, 63122 St Genès Champanelle, France.

The Biochemical Journal
|June 21, 2001
PubMed

Insights

Glucose (Glc) regulates protein breakdown in cancer cells. Lysosomal proteases, not proteasomes, are key to this Glc-dependent control of protein turnover in transformed cells.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Cancer Research

Background:

  • Transformed cells encounter diverse microenvironments, including low glucose (Glc) levels within tumors.
  • Impaired protein turnover is common in transformed cells, but the influence of Glc remains unclear.

Purpose of the Study:

  • To investigate the role of glucose (Glc) in regulating protein turnover in ras-transformed fibroblasts (KBALB).
  • To identify the specific proteolytic systems involved in Glc-mediated protein turnover control.

Main Methods:

  • Assessing protein breakdown rates in KBALB cells under varying glucose concentrations.
  • Analyzing the impact of specific protease inhibitors (Lactacystin, E-64d, methylamine) on proteolysis.
  • Quantifying the levels of lysosomal cathepsins (B, L, D) and other proteases (calpains, proteasome subunits).

Main Results:

  • Glucose (Glc) was found to significantly control protein turnover in ras-transformed fibroblasts.
  • Glc-dependent regulation of protein breakdown correlated with changes in lysosomal cathepsins B, L, and D levels.
  • Autophagic sequestration and non-lysosomal proteolytic systems were unaffected by glucose levels.
  • Inhibition of lysosomal cysteine and aspartic endopeptidases by methylamine prevented the Glc-dependent increase in proteolysis.

Conclusions:

  • Glucose (Glc) plays a critical role in regulating protein turnover in transformed cells.
  • The lysosomal proteolytic system is primarily responsible for glucose-mediated control of intracellular proteolysis.

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