Caspases‐2 and ‐8 are involved in the presenilin1/γ‐secretase‐dependent cleavage of amyloid precursor protein after the induction of apoptosis
Copyright policy )Caspases‐2 and ‐8 are involved in the presenilin1/γ‐secretase‐dependent cleavage of amyloid precursor protein after the induction of apoptosis
AbstractThe presenilin/γ‐secretase protease cleaves many type‐I membrane proteins, including the amyloid β‐protein (Aβ) precursor (APP). Previous studies have shown that apoptosis induces alterations in Aβ production in a caspase‐dependent manner. Here, we report that staurosporine (STS)‐induced apoptosis induces caspase‐8 and/or‐2‐dependent γ‐secretase activation. Blocking of caspase activity with caspase‐8 inhibitor z‐IETD‐fmk, and caspase‐2 inhibitor z‐VDVAD‐fmk reduced Aβ 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 Aβ production by STS. This finding was further supported by evidence that siRNA transfection, depleting caspase‐2 or ‐8 levels, lowered Aβ production in HSW and H4‐C99 cells without affecting expression of APP or γ‐secretase complex. In addition, Aβ production by STS was decreased by JNK inhibitors, SP600125. These results suggest that caspase‐2 and/or ‐8 is involved in presenilin/γ‐secretase activation and Aβ production in apoptosis. © 2010 Wiley‐Liss, Inc.
- National Institutes of Health Malaysia
Anthracenes, Caspase 8, Caspase 2, JNK Mitogen-Activated Protein Kinases, Apoptosis, Receptors, Cell Surface, Cysteine Proteinase Inhibitors, Caspase Inhibitors, Protease Nexins, Amyloid beta-Protein Precursor, Cysteine Endopeptidases, Caspases, Cell Line, Tumor, Mutation, Presenilin-1, Humans, Amyloid Precursor Protein Secretases, Enzyme Inhibitors, RNA, Small Interfering, Oligopeptides
Anthracenes, Caspase 8, Caspase 2, JNK Mitogen-Activated Protein Kinases, Apoptosis, Receptors, Cell Surface, Cysteine Proteinase Inhibitors, Caspase Inhibitors, Protease Nexins, Amyloid beta-Protein Precursor, Cysteine Endopeptidases, Caspases, Cell Line, Tumor, Mutation, Presenilin-1, Humans, Amyloid Precursor Protein Secretases, Enzyme Inhibitors, RNA, Small Interfering, Oligopeptides
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