title: GD3-7-aldehyde is an apoptosis inducer and interacts with adenine nucleotide translocase.
abstract: 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.
authors.affiliation: University of Versailles-SQY, PRES UniverSud Paris, CNRS UMR8159, 45 Avenue des Etats-Unis, 78035 Versailles, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Brenner
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kniep
authors.forename: Evelyne
authors.initials: E
authors.lastname: Maillier
authors.forename: Cécile
authors.initials: C
authors.lastname: Martel
authors.forename: Claudia
authors.initials: C
authors.lastname: Franke
authors.forename: Nadja
authors.initials: N
authors.lastname: Röber
authors.forename: Michael
authors.initials: M
authors.lastname: Bachmann
authors.forename: Ernst Peter
authors.initials: EP
authors.lastname: Rieber
authors.forename: Roger
authors.initials: R
authors.lastname: Sandhoff
mesh_terms: 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
chemical_list: D005732:Gangliosides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C026226:ganglioside, GD3; D016572:Cyclosporine; D000226:Mitochondrial ADP, ATP Translocases