Effect of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide (PK11195), a specific ligand of the peripheral benzodiazepine receptor, on the lipid fluidity of mitochondria in human glioma cells

When human glioma cells were incubated for 24 hr in serum-free medium with nanomolar concentrations of 1-(2-chlorophenyl)-N-methyl-N( 1-methylpropyl)- 3-isoquinoline carboxamide (PK11195), a specific ligand of the peripheral b enzodiazepine receptor (PBR), a significant increase in the membrane fluidi ty of mitochondria isolated from these cells was registered. These effects were not observed with a shorter incubation time (2 hr) of the cells with P K11195 nor in the presence of serum. Other significant associated changes w ere observed: a significant increase of 16 +/- 4% of [H-3]thymidine incorpo ration into DNA was detected in cells in the presence of PK11195 in serum f ree medium, and an increase of 33 +/- 5% as compared to controls in nonyl a cridine orange uptake, as indicator of mitochondrial mass, was also registe red in cells treated with 10 nM PK11195. [H-3]PK11195 binding was decreased in cells incubated with PK11195; a 45% decrease compared to controls was o btained. In view of the effect of PER ligands on DNA synthesis, changes in mitochondrial lipid metabolism through interaction with PBRs might lead to biogenesis of mitochondria to support the increased metabolic requirements for cell division, which is even higher in malignant cells. (C) 1999 Elsevi er Science Inc.