β-Amyloid induces nuclear protease-mediated lamin fragmentation independent of caspase activation
In: Biochimica et biophysica acta, Jg. 1863 (2015-08-21), Heft 6 Pt
Online
unknown
Zugriff:
β-Amyloid (Aβ), a hallmark peptide of Alzheimer's disease, induces both caspase-dependent apoptosis and non-apoptotic cell death. In this study, we examined caspase-independent non-apoptotic cell death preceding caspase activation in Aβ42-treated cells. We first determined the optimal treatment conditions for inducing cell death without caspase activation and selected a double-treatment method involving the incubation of cells with Aβ42 for 4 and 6 h (4+6 h sample). We observed that levels of lamin A (LA) and lamin B (LB) were reduced in the 4+6 h samples. This reduction was decreased by treatment with suc-AAPF-CMK, an inhibitor of nuclear scaffold (NS) protease, but not by treatment with z-VAD-FMK, a pan-caspase inhibitor. In addition, suc-AAPF-CMK decreased the changes in nuclear morphology observed in cells in the 4+6 h samples, which were different from nuclear fragmentation observed in STS-treated cells. Furthermore, suc-AAPF-CMK inhibited cell death in the 4+6 h samples. LA and LB fragmentation occurred in the isolated nuclei and was also inhibited by suc-AAPF-CMK. Together, these data indicated that the fragmentation of LA and LB in the Aβ42-treated cells was induced by an NS protease, whose identity is not clearly determined yet. A correlation between Aβ42 toxicity and the lamin fragmentation by NS protease suggests that inhibition of the protease could be an effective method for controlling the pathological process of AD.
Titel: |
β-Amyloid induces nuclear protease-mediated lamin fragmentation independent of caspase activation
|
---|---|
Autor/in / Beteiligte Person: | Vijay Sankar Ramasamy ; Park, Il-Seon ; Md. Aminul Haque ; Md. Imamul Islam ; Song Yub Shin |
Link: | |
Zeitschrift: | Biochimica et biophysica acta, Jg. 1863 (2015-08-21), Heft 6 Pt |
Veröffentlichung: | 2015 |
Medientyp: | unknown |
ISSN: | 0006-3002 (print) |
Schlagwort: |
|
Sonstiges: |
|