Acid sphingomyelinase is indispensable for UV light-induced Bax conformational change at the mitochondrial membrane
| Autor: | Katja Wiegmann, Hamid Kashkar, Dirk Haubert, Martin Krönke, Benjamin Yazdanpanah |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Programmed cell death
Conformational change Protein Conformation Ultraviolet Rays Green Fluorescent Proteins Fluorescent Antibody Technique Gene Expression Apoptosis Ceramides Biochemistry Mitochondrial apoptosis-induced channel Cathepsin D medicine Humans RNA Small Interfering Inner mitochondrial membrane Molecular Biology bcl-2-Associated X Protein Niemann-Pick Diseases Caspase 8 biology Cell-Free System Caspase 3 Cytochrome c Cell Membrane Cytochromes c Cell Biology Cell biology Mitochondria Sphingomyelin Phosphodiesterase Proto-Oncogene Proteins c-bcl-2 Caspases biology.protein Apoptotic signaling pathway Acid sphingomyelinase medicine.drug HeLa Cells Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 280(21) |
| ISSN: | 0021-9258 |
| Popis: | Ultraviolet light-induced apoptosis can be caused by DNA damage but also involves immediate-early cell death cascades characteristic of death receptor signaling. Here we show that the UV light-induced apoptotic signaling pathway is unique, targeting Bax activation at the mitochondrial membrane independent of caspase-8 or cathepsin D activity. Cells deficient in acid sphingomyelinase (ASMase) do not show UV light-induced Bax activation, cytochrome c release, or apoptosis. In ASMase-deficient cells, the apoptotic UV light response is restored by stable or transient expression of human ASMase. Bax conformational change in ASMase-/- cells is also caused by synthetic C16-ceramide acting on intact cells or isolated mitochondria. The results suggest that UV light-triggered ASMase activation is essentially required for Bax conformational change leading to mitochondrial release of pro-apoptotic factors like cytochrome c and Smac. |
| Databáze: | OpenAIRE |
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