GD3-7-aldehyde is an apoptosis inducer and interacts with adenine nucleotide translocase.
We prepared GD3-7-aldehyde (GD3-7) and determined its apoptotic potential. GD3-7 proved to be more efficient to induce pro-apoptotic mitochondrial alterations than GD3 when tested on mouse liver mitochondria. GD3-7-induced mitochondrial swelling and depolarization was blocked by cyclosporin A (CsA) supporting a critical role of the permeability transition pore complex (PTPC) during GD3-7-mediated apoptosis. In contrast to GD3, GD3-7 was able to induce channel formation in proteoliposomes containing adenine nucleotide translocase (ANT). This suggests that ANT is the molecular target of GD3-7. Using a specific antiserum, GD3-7 was detected in the lipid extract of the myeloid tumor cell line HL-60 after apoptosis induction, but not in living cells. Therefore, GD3-7 might be a novel mediator of PTPC-dependent apoptosis in cancer cells.
Brenner
Catherine
C
University of Versailles-SQY, PRES UniverSud Paris, CNRS UMR8159, 45 Avenue des Etats-Unis, 78035 Versailles, France.
Kniep
Bernhard
B
Maillier
Evelyne
E
Martel
Cécile
C
Franke
Claudia
C
Röber
Nadja
N
Bachmann
Michael
M
Rieber
Ernst Peter
EP
Sandhoff
Roger
R
D000818:Animals; D017209:Apoptosis; D016572:Cyclosporine / Q000494:pharmacology; D005732:Gangliosides / Q000378:metabolism* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling
D005732:Gangliosides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C026226:ganglioside, GD3; D016572:Cyclosporine; D000226:Mitochondrial ADP, ATP Translocases