Caspases-2 and -8 are involved in the presenilin1/gamma-secretase-dependent cleavage of amyloid precursor protein after the induction of apoptosis
| Autor: | San Sook Chae, Young Ho Koh, Chulman Jo, Sang-Moon Yun, Chul Bae Yoo, Sangmee Ahn Jo |
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| Rok vydání: | 2010 |
| Předmět: |
Caspase 2
Apoptosis Receptors Cell Surface Cysteine Proteinase Inhibitors Transfection Presenilin Cellular and Molecular Neuroscience Amyloid beta-Protein Precursor Cell Line Tumor mental disorders Amyloid precursor protein medicine Presenilin-1 Staurosporine Humans Enzyme Inhibitors RNA Small Interfering Caspase Gamma secretase Anthracenes Caspase 8 biology P3 peptide JNK Mitogen-Activated Protein Kinases Molecular biology Caspase Inhibitors nervous system diseases Cell biology Protease Nexins Cysteine Endopeptidases Caspases Mutation biology.protein Amyloid Precursor Protein Secretases Amyloid precursor protein secretase Oligopeptides medicine.drug |
| Zdroj: | Journal of neuroscience research. 88(9) |
| ISSN: | 1097-4547 |
| Popis: | The presenilin/gamma-secretase protease cleaves many type-I membrane proteins, including the amyloid beta-protein (Abeta) precursor (APP). Previous studies have shown that apoptosis induces alterations in Abeta production in a caspase-dependent manner. Here, we report that staurosporine (STS)-induced apoptosis induces caspase-8 and/or-2-dependent gamma-secretase activation. Blocking of caspase activity with caspase-8 inhibitor z-IETD-fmk, and caspase-2 inhibitor z-VDVAD-fmk reduced Abeta production by STS in H4 cells expressing the Swedish mutant of APP (HSW) or APP-C99 (H4-C99). There was no inhibitory effect of other caspases (-1, -3, -5, -6, -9) on Abeta production by STS. This finding was further supported by evidence that siRNA transfection, depleting caspase-2 or -8 levels, lowered Abeta production in HSW and H4-C99 cells without affecting expression of APP or gamma-secretase complex. In addition, Abeta production by STS was decreased by JNK inhibitors, SP600125. These results suggest that caspase-2 and/or -8 is involved in presenilin/gamma-secretase activation and Abeta production in apoptosis. |
| Databáze: | OpenAIRE |
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