title: Amyloid β binds procaspase-9 to inhibit assembly of Apaf-1 apoptosome and intrinsic apoptosis pathway.
abstract: Apoptosis is essential in the death process induced by Amyloid-β (Aβ), a major constituent of diffuse plaques found in Alzheimer's disease patients. However, we have found that caspase activation and cell death induced by staurosporine, employed to induce the intrinsic mitochondria-dependent apoptotic pathway, were significantly reduced by 42 amino-acid Aβ42, implying that the peptide also has a negative effect on the apoptotic process. The inhibitory effect of Aβ42 on the apoptotic pathway is associated with its interaction with procaspase-9 and consequent inhibition of Apaf-1 apoptosome assembly. We detected the inhibitory effect in the early stage (<8h) of apoptosis, but later caspase activation becomes obvious. Thus we inferred that the inhibitory process on apoptosis begins at an early stage, and the later robust activation surpasses it. We propose that the apoptotic manifestation in Aβ-treated cells is a combined consequence of those anti- and pro-apoptotic processes.
authors.affiliation: Department of Bio-Materials Engineering, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea; Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh.
authors.forename: Md Golam
authors.initials: MG
authors.lastname: Sharoar
authors.affiliation: Department of Bio-Materials Engineering, College of Medicine, 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, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea; Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin St., Houston, TX, USA.
authors.forename: Md
authors.initials: M
authors.lastname: Shahnawaz
authors.affiliation: Department of Bio-Materials Engineering, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea; Cellular and Molecular Medicine, College of 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, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea; Cellular and Molecular Medicine, College of 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: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D053478:Apoptosomes / Q000737:chemistry / Q000648:ultrastructure; D053477:Apoptotic Protease-Activating Factor 1 / Q000737:chemistry / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism*; D002474:Cell-Free System; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology
chemical_list: C506592:APAF1 protein, human; D016229:Amyloid beta-Peptides; D053478:Apoptosomes; D053477:Apoptotic Protease-Activating Factor 1; D053148:Caspase 3; D053453:Caspase 9; D019311:Staurosporine
keywords: Amyloid-β; Apoptosis; Apoptosome; Caspase; Intrinsic apoptosis pathway