How does caspase-1 cause apoptosis?
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.
What is the role of caspase-1?
Caspase-1 modulates inflammatory and host defense responses against microbial pathogens by processing the precursor forms of the pro-inflammatory cytokines IL-1β and IL-18 into their biologically active forms (Kuida et al., 1995; Li et al., 1995; Ghayur et al., 1997; Gu et al., 1997).
What happens when caspase-1 is activated?
Pyroptosis response Following the inflammatory response, an activated Caspase-1 can induce pyroptosis, a lytic form of cell death, depending on the signal received as well as the specific inflammasome sensor domain protein that received it.
Is caspase-1 secreted?
Inflammatory protease, caspase-1, is secreted from monocytes in a stably active form in response to inflammasome activation (INM3P.
How does caspase-1 cause pyroptosis?
Pyroptosis is triggered by Caspase-1 after its activation by various inflammasomes, and results in lysis of the affected cell. Both pyroptosis and apoptosis are programmed cell death mechanisms, but are dependent on different caspases, unlike oncosis.
What is the caspase cascade?
Caspases are a family of cysteine proteases that act in concert in a cascade triggered by apoptosis signaling. The culmination of this cascade is the cleavage of a number of proteins in the cell, followed by cell disassembly, cell death, and, ultimately, the phagocytosis and removal of the cell debris.
Where does caspase cleave?
Caspase-1 cleaves the prodomain from inactive pro-IL-1β at YVHD(119)-A, producing bioactive IL-1β (31,32). Characterization of caspase-1 -deficient mice confirmed that caspase-1 plays a major role in vivo in activation of IL-1β (33,34).
How do I activate caspase-1?
Activation of caspase-1 through NLRC4 leads to the processing and secretion of IL-1β and IL-18 as well as other activities. Caspase-1 activation by means of NLRC4 is TLR5 independent in that it proceeds unabated in TLR5-deficient macrophages28,29,35.
Is caspase secreted?
Facts. Caspase-1 cleaves the pro-inflammatory cytokine pro-interleukin (IL)-1β to an active secreted molecule in monocytes and macrophages. Pyroptosis is a caspase-1-mediated macrophage cell death following infection by intracellular pathogens as part of the host response.
Is pyroptosis caspase dependent?
Pyroptosis is regulated via a caspase-1-dependent or caspase-1-independent mechanism (Figure 2). Caspase-1-independent pyroptosis is executed by human caspase-4, human caspase-5 or mouse caspase-11 (39).
What is the difference between apoptosis and pyroptosis?
Pyroptosis, as a form of programmed cell death, has many morphological differences as compared to apoptosis. Both pyroptosis and apoptosis undergo chromatin condensation, but during apoptosis, the nucleus breaks into multiple chromatin bodies; in pyroptosis, the nucleus remains intact.
What is the role of caspase in apoptosis?
Apoptosis: Caspase Pathways. A group of intracellular proteases called caspases are responsible for the deliberate disassembly of the cell into apoptotic bodies during apoptosis.1 Caspases are present as inactive pro-enzymes that are activated by proteolytic cleavage.
What happens when caspase 8 is removed from the cell?
Inactivation of caspases blocks apoptosis but switches the cell fate to a form of programmed necrotic death called necroptosis. Deletion of the components of the extrinsic apoptosis pathway such as caspase-8 or FADD results in TNF-induced necrotic cell death (60).
Is caspase 3-dependent apoptosis involved in brain development in mice?
Caspase 9 -/- mice often developed brain tissue outside the skull. This difference suggests that both caspase 9-, caspase 3-dependent (Fig. 1A) and caspase 9-dependent, caspase 3-independent (Fig. 1C) apoptosis pathways are involved in brain development.
Does the NLRP3 inflammasome activate caspase 1 during apoptosis?
However, activation of caspase-1 by the NLRP3 inflammasome during apoptosis is ambiguous. During intrinsic apoptosis, caspase-3 and -7 are proposed to induce K+efflux and NLRP3 activation, which in turn activates caspase-1-dependent activation of IL-1β (162, 163).