title: β-Amyloid induces nuclear protease-mediated lamin fragmentation independent of caspase activation.
abstract: 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.
authors.affiliation: Department of Bio-Materials Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Vijay Sankar
authors.initials: VS
authors.lastname: Ramasamy
authors.affiliation: Department of Bio-Materials Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Md Imamul
authors.initials: MI
authors.lastname: Islam
authors.affiliation: Department of Bio-Materials Engineering, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Md Aminul
authors.initials: MA
authors.lastname: Haque
authors.affiliation: Department of Bio-Materials Engineering, Chosun University, Gwangju 501-759, Republic of Korea; Cellular and Molecular Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Song Yub
authors.initials: SY
authors.lastname: Shin
authors.affiliation: Department of Bio-Materials Engineering, Chosun University, Gwangju 501-759, Republic of Korea; Cellular and Molecular Medicine, Chosun University, Gwangju 501-759, Republic of Korea. Electronic address: parkis@chosun.ac.kr.
authors.forename: Il-Seon
authors.initials: IS
authors.lastname: Park
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D034904:Lamin Type A / Q000378:metabolism*; D034921:Lamin Type B / Q000378:metabolism*; D018613:Microscopy, Confocal; D010446:Peptide Fragments / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D061945:Caspase Inhibitors; D034904:Lamin Type A; D034921:Lamin Type B; D010446:Peptide Fragments; D011480:Protease Inhibitors; D010450:Endopeptidases; D020169:Caspases; C095820:lamin proteinase; D019311:Staurosporine
keywords: Alzheimer's disease; Apoptosis; Caspase; Lamin; Nuclear scaffold protease; β-amyloid