RRC ID 57781
Author Tsuchiya K, Nakajima S, Hosojima S, Thi Nguyen D, Hattori T, Manh Le T, Hori O, Mahib MR, Yamaguchi Y, Miura M, Kinoshita T, Kushiyama H, Sakurai M, Shiroishi T, Suda T.
Title Caspase-1 initiates apoptosis in the absence of gasdermin D.
Journal Nat Commun
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.
Volume 10(1)
Pages 2091
Published 2019-5-7
DOI 10.1038/s41467-019-09753-2
PII 10.1038/s41467-019-09753-2
PMID 31064994
PMC PMC6505044
MeSH Animals Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism* BH3 Interacting Domain Death Agonist Protein / genetics BH3 Interacting Domain Death Agonist Protein / metabolism Caspase 1 / physiology* Caspase 3 / metabolism Caspase 9 / metabolism Cell Line, Tumor Cerebral Cortex / cytology Embryo, Mammalian Gene Knockout Techniques Inflammasomes / immunology* Macrophages / cytology Macrophages / immunology Macrophages / microbiology Mice Mice, Inbred C57BL Neurons / drug effects Neurons / physiology Nigericin / pharmacology Primary Cell Culture Pyroptosis / drug effects Pyroptosis / immunology* RAW 264.7 Cells Receptors, Estrogen / metabolism* Salmonella typhimurium / immunology
IF 11.878
Times Cited 35
Human and Animal Cells Colon-26(RCB2657)