Sharoar Md Golam, Islam Md Imamul, Shahnawaz Md, Shin Song Yub, Park Il-Seon
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.
Department of Bio-Materials Engineering, College of Medicine, Chosun University, Gwangju 501-759, Republic of Korea.
Biochim Biophys Acta. 2014 Apr;1843(4):685-93. doi: 10.1016/j.bbamcr.2014.01.008. Epub 2014 Jan 12.
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.
细胞凋亡在由β-淀粉样蛋白（Aβ）诱导的死亡过程中至关重要，Aβ是阿尔茨海默病患者脑中弥漫性斑块的主要成分。然而，我们发现，用于诱导内源性线粒体依赖性凋亡途径的星形孢菌素所诱导的半胱天冬酶激活和细胞死亡，被42个氨基酸的Aβ42显著降低了42%，这意味着该肽对凋亡过程也有负面影响。Aβ42对凋亡途径的抑制作用与其与procaspase-9的相互作用以及随后对Apaf-1凋亡小体组装的抑制有关。我们在凋亡早期（<8小时）检测到了这种抑制作用，但后期半胱天冬酶激活变得明显。因此我们推断，对凋亡的抑制过程始于早期，而后期强烈的激活超过了它。我们提出，Aβ处理的细胞中的凋亡表现是这些抗凋亡和促凋亡过程的综合结果。
