细胞凋亡
半胱氨酸蛋白酶
细胞色素c
细胞生物学
凋亡体
内源性凋亡
葡萄孢霉素
生物
程序性细胞死亡
半胱氨酸蛋白酶-9
半胱氨酸蛋白酶3
信号转导
线粒体
分子生物学
化学
生物化学
蛋白激酶C
作者
Md. Imamul Islam,Golam Sharoar,Eun-Kyoung Ryu,Il‐Seon Park
标识
DOI:10.3892/ijmm.2017.3193
摘要
Amyloid-β (Aβ), a main pathogenic factor of Alzheimer's disease (AD), induces apoptosis accompanied by caspase activation. However, limited caspase activation and the suppression of the intrinsic apoptotic pathway (IAPW) are frequently observed upon Aβ treatment. In this study, we investigated whether these suppressive effects of Aβ can be overcome; we also examined the death-related pathways. Single treatments of cells with Aβ42 for up to 48 h barely induced caspase activation. In cells treated with Aβ42 twice for 2 h followed by 22 h (2+22 h) or for longer durations, the apoptotic protease activating factor-1 (Apaf-1) apoptosome was formed and caspases-3 and -9 were activated to a certain extent, suggesting the activation of the IAPW. However, the Aβ42-induced activation of the IAPW differed from that induced by treatment with other agents, such as staurosporine (STS) in that lower amounts of cytochrome c were released from the mitochondria, the majority of procaspase-9 in the Apaf-1 complex was not processed and caspase-3 was activated to a lesser extent in the peptide-treated cells. Thus, it seemed that the IAPW was not fully activated by Aβ42. The 30- and 41/43-kDa fragments derived from procaspase-8 were detected, which appear to be produced through the IAPW without death-inducing signaling-complex (DISC) formation, a key feature of the extrinsic apoptotic pathway (EAPW). Bid cleavage was observed only after caspase-3 activity reached its maximal levels, suggesting that the cleavage may contribute in a limited capacity to the amplification process of the IAPW in the Aβ-treated cells. Taken together, our data suggest that the IAPW, albeit functional only to a limited extent, plays a major role in Aβ42-induced apoptosis without the EAPW.
科研通智能强力驱动
Strongly Powered by AbleSci AI