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GD3-7-aldehyde is an apoptosis inducer and interacts with adenine nucleotide translocase |
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| Authors: | Catherine Brenner Bernhard Kniep Evelyne Maillier Claudia Franke Michael Bachmann Roger Sandhoff |
| Affiliation: | a University of Versailles-SQY, PRES UniverSud Paris, CNRS UMR8159, 45, Avenue des Etats-Unis, 78035 Versailles, France b Technical University of Dresden, Institute of Immunology, Medical Faculty Carl Gustav Carus, Fetscherstr. 74, 01307 Dresden, Germany c German Cancer Research Center, Department of Cellular and Molecular Pathology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany |
| 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. |
| Keywords: | amu, atomic mass units ANT, adenine nucleotide translocase CAT, carboxyatractyloside CsA, cyclosporin A CypD, cyclophilin D ΔΨm, mitochondrial transmembrane potential MMP, mitochondrial membrane permeabilization PT, permeabilty transition PTPC, permeability transition pore complex VDAC, voltage-dependent anion channel 4-MUP, 4-methyl umbelliferyl phosphate GM3, II3NeuAc-LacCer GD3, II3(NeuAc)2-LacCer GD3-7, GD3-7-aldehyde AcGD3, 9-O-acetyl GD3 |
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