Peripheral benzodiazepine induces morphological changes and proliferation of mitochondria in glioma cells.
Peripheral benzodiazepine (PBD) receptors are localized on the mitochondrial membrane and are highly expressed in brain tumors compared to normal brain. To elucidate the biological role of the PBD receptor on mitochondria, we examined the effect of PBDs on mitochondrial morphology in C6 and T98G glioma cells using rhodamine 123 and quantitative electron microscopy. In cells incubated in serum-free medium alone, mitochondria were distributed in a filamentous pattern throughout the cytoplasm. By contrast, the mitochondria aggregated in the perinuclear region in PK11195 or Ro5-4864 (10 nM) treated cells. Quantitative electron micrography revealed a 250% increased in the number of mitochondria with elongated cristae and a fivefold increase in dividing mitochondria in PK11195-treated cells compared with cells incubated in serum-free medium alone. PBD treatment also resulted in vacuolation within the matrix and mitochondrial swelling. These data suggest that PBDs influence mitochondrial morphology and induce mitochondrial replication in cultured glioma cells.
Shiraishi
T
T
Brain Research Institute, Jonsson Cancer Center, Los Angeles, California.
Black
K L
KL
Ikezaki
K
K
Becker
D P
DP
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002460:Cell Line; D002998:Clonazepam / Q000494:pharmacology*; D016895:Culture Media, Serum-Free; D005456:Fluorescent Dyes; D005910:Glioma / Q000473:pathology* / Q000648:ultrastructure; D007546:Isoquinolines / Q000494:pharmacology*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D020112:Rhodamine 123; D012235:Rhodamines
D001570:Benzodiazepinones; D016895:Culture Media, Serum-Free; D005456:Fluorescent Dyes; D007546:Isoquinolines; D011963:Receptors, GABA-A; D012235:Rhodamines; D020112:Rhodamine 123; C028513:4'-chlorodiazepam; D002998:Clonazepam; C037850:PK 11195