Similar pyruvate kinase modifications in glioblastoma cells by 7β-hydroxycholesterol and glutamine withdrawal

Jan de Weille; Christine Fabre; Camille Gaven; Norbert Bakalara

doi:10.1016/j.bcp.2013.03.012

Similar pyruvate kinase modifications in glioblastoma cells by 7β-hydroxycholesterol and glutamine withdrawal

Biochem Pharmacol. 2013 Jul 1;86(1):161-7. doi: 10.1016/j.bcp.2013.03.012. Epub 2013 Mar 26.

Authors

Jan de Weille¹, Christine Fabre, Camille Gaven, Norbert Bakalara

Affiliation

¹ Institut des Neurosciences de Montpellier, U1051 INSERM, 80 rue Augustin Fliche, 34295 Montpellier cedex 05, France. [email protected]

PMID: 23537700
DOI: 10.1016/j.bcp.2013.03.012

Abstract

Oxysterols possess anti-proliferative properties that may be used with much effect in the treatment of cancer. We have demonstrated previously that 7 beta-hydroxycholesterol (7b-HC) provokes both metabolic stress, as witnessed by AMPK activation, and changes in lipid raft composition in C6 glioblastoma cells. These observations suggested that glycolysis might have been changed. Here we will show that 7b-HC increases cell cycle time and that it changes the affinity of pyruvate kinase to its substrate, phosphoenol pyruvate. The latter effect is mimicked by glutamine withdrawal.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinases / metabolism
Animals
Brain Neoplasms / metabolism*
Brain Neoplasms / pathology
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Cyclin D1 / metabolism
Cyclin E / metabolism
Enzyme Activation
Glioblastoma / metabolism*
Glioblastoma / pathology
Glutamine / metabolism*
Glycolysis
Hydroxycholesterols / metabolism*
Hydroxycholesterols / pharmacology
Phosphoenolpyruvate / metabolism
Pyruvate Kinase / metabolism
Rats
Stress, Physiological

Substances

Cyclin E
Hydroxycholesterols
Glutamine
Cyclin D1
cholest-5-en-3 beta,7 alpha-diol
Phosphoenolpyruvate
Pyruvate Kinase
AMP-Activated Protein Kinases