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.
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Authors | Catherine Brenner, Bernhard Kniep, Evelyne Maillier, Cécile Martel, Claudia Franke, Nadja Röber, Michael Bachmann, Ernst Peter Rieber, Roger Sandhoff |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 391
Issue 1
Pg. 248-53
(Jan 01 2010)
ISSN: 1090-2104 [Electronic] United States |
PMID | 19912988
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2009 Elsevier Inc. All rights reserved. |
Chemical References |
- Gangliosides
- Mitochondrial Membrane Transport Proteins
- Mitochondrial Permeability Transition Pore
- ganglioside, GD3
- Cyclosporine
- Mitochondrial ADP, ATP Translocases
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Topics |
- Animals
- Apoptosis
- Cyclosporine
(pharmacology)
- Gangliosides
(metabolism, pharmacology)
- HL-60 Cells
- Humans
- Mice
- Mitochondria, Liver
(drug effects, enzymology)
- Mitochondrial ADP, ATP Translocases
(metabolism)
- Mitochondrial Membrane Transport Proteins
(drug effects, metabolism)
- Mitochondrial Permeability Transition Pore
- Mitochondrial Swelling
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