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: 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)
• 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

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