上睑下垂
细胞凋亡
细胞生物学
程序性细胞死亡
炎症体
半胱氨酸蛋白酶1
半胱氨酸蛋白酶
尼日利亚霉素
化学
半胱氨酸蛋白酶8
半胱氨酸蛋白酶3
坏死
NLRP1
生物
生物化学
受体
遗传学
膜
作者
Kazuo Tsuchiya,Shinsuke Nakajima,Shoko Hosojima,Dinh Thi Nguyen,Tsuyoshi Hattori,Thuong Manh Le,Osamu Hori,Mamunur Rashid Mahib,Yoshifumi Yamaguchi,Masayuki Miura,Takeshi Kinoshita,Hiroko Kushiyama,Minoru Sakurai,Toshihiko Shiroishi,Takafumi Suda
标识
DOI:10.1038/s41467-019-09753-2
摘要
Abstract Caspase-1 activated in inflammasomes triggers a programmed necrosis called pyroptosis, which is mediated by gasdermin D (GSDMD). However, GSDMD-deficient cells are still susceptible to caspase-1-mediated cell death. Therefore, here, we investigate the mechanism of caspase-1-initiated cell death in GSDMD-deficient cells. Inflammasome stimuli induce apoptosis accompanied by caspase-3 activation in GSDMD-deficient macrophages, which largely relies on caspase-1. Chemical dimerization of caspase-1 induces pyroptosis in GSDMD-sufficient cells, but apoptosis in GSDMD-deficient cells. Caspase-1-induced apoptosis involves the Bid-caspase-9-caspase-3 axis, which can be followed by GSDME-dependent secondary necrosis/pyroptosis. However, Bid ablation does not completely abolish the cell death, suggesting the existence of an additional mechanism. Furthermore, cortical neurons and mast cells exhibit little or low GSDMD expression and undergo apoptosis after oxygen glucose deprivation and nigericin stimulation, respectively, in a caspase-1- and Bid-dependent manner. This study clarifies the molecular mechanism and biological roles of caspase-1-induced apoptosis in GSDMD-low/null cell types.
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