The Immunohistochemistry Antibody Company
Caspases, or Cysteine Aspartate-specific Proteases, are enzymes involved in the signal transduction pathways of apoptosis and inflammation. Caspases are produced in cells as catalytically inactive zymogens which experience proteolytic processing at conserved aspartic residues. Upon cleavage, they produce a large and a small subunit that dimerize to form the active enzyme. The sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. There are two types of apoptotic caspases, initiator (apical) caspases and effector (executioner) caspases. Initiator caspases, such as Caspase-2, -8, -9, and -10, cleave inactive pro-forms of effector caspases, thereby activating them. Effector caspases, such as Caspase-3, -6, and -7, in turn cleave other protein substrates within the cell, to trigger the apoptotic process. The initiation of this cascade reaction is regulated by caspase inhibitors. Caspase-4 and Caspase-5, which are overexpressed in some cases of vitiligo and associated autoimmune diseases caused by NALP1 variants, are not currently classified as initiator or effector in MeSH, because they are inflammatory enzymes that, in concert with Caspase-1, are involved in T-cell maturation. Caspase-14 is not involved in apoptosis or inflammation, but instead is involved in skin cell development.
Caspase antibodies are available from LSBio for all 12 caspases that have been identified in humans. Caspase antibodies are used in many applications, particularly in immunohistochemistry to detect activation of Caspase-3 in apoptosis.
Anti-Caspase-1 antibody LS-B112
Anti-Caspase-2 antibody LS-B475
Anti-Caspase-3 antibody LS-B3404
Anti-Caspase-4 antibody LS-B710
Anti-Caspase-5 antibody LS-B476
Anti-Caspase-6 antibody LS-B1345
Anti-Caspase-7 antibody LS-B3670
Anti-Caspase-8 antibody LS-B3796
Anti-Caspase-10 antibody LS-C49364
Anti-Caspase-12 antibody LS-747
Anti-Caspase-14 antibody LS-B474
Caspases, or Cysteine Aspartate-specific Proteases, are enzymes involved in the signal transduction pathways of apoptosis and inflammation. Caspases are produced in cells as catalytically inactive zymogens which experience proteolytic processing at conserved aspartic residues. Upon cleavage, they produce 2 subunits, large and small, that dimerize to form the active enzyme. The sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. There are more than 400 caspases so far identified, and they are divided into two major classes: effectors and initiators.
Effector caspases, also known as executioner caspases, include Caspase-3, -6, and -7, and are responsible for cleaving downstream substrates. Both Caspase-3 and -7 play important roles in apoptosis, where they are activated and enhanced by initiator caspases and are responsible for proteolytic degradation and the eventual death of a cell.
Initiator caspases, also known as apical caspases, include Caspase-1, -2, -4, -5, -8, -9, -10, and -12, and both interact with and are activated by upstream adaptor molecules through Caspase Activation Recruitment Domains and Death Effector Domains, both of which are protein-protein interaction domains. Initiator caspases activate downstream effector caspases in a "cascade" during the cell death process of apoptosis.
Caspases play a vital role in programmed cell death, apoptosis. Apoptosis is carried out by a "Caspase cascade" that is activated by two pathways, the Intrinsic (mitochondrial) pathway and the Extrinsic (death receptor) pathway:
The Intrinsic Pathway:
The intrinsic pathway primarily involves mitochondrial outer membrane permeabilization, and its purpose is to initiate apoptosis upon reception of cellular stress signals (e.g. in the case of damage to DNA). The mitochondrion plays a role as an intracellular death receptor by receiving a number of proapoptotic signals which trigger oligomerization of proapoptotic proteins. When the stability of a mitochondrial membrane is disturbed, these proteins, namely Bax and Bak, are released, leading to the activation of initiator caspases to begin the caspase cascade. Bax is a Bcl-2-associated protein, while Bak is a Bcl-2-antagonist killer, and they cause membrane permeabilization through destabilization of the lipid bilayer. This process leads to the release of cytochrome c into the cytoplasm, a signal for the formation of Apaf1-containing apoptosomes, which bind and activate initiator procaspase-9. Caspase-9, upon maturation, is still bound to this apoptosome, now a holo-enzyme complex that in turn activates downstream effector Caspases -3 and -7. The intra-chain cleavage of the effector Caspase-3 or -7 by initiator Caspase-9 greatly enhances the effectors' catalytic activity, leading to cell degredation and death.
The Extrinsic Pathway:
The cell death (extrinsic) pathway is characterized by the elimination of unwanted cells during development. In this pathway, the ligand for death receptor Fas triggers the Death-Inducing Signaling Complex (DISC) at the cell membrane. This complex is responsible for the recruitment of initiator Caspase-8, which is consequently cleaved in procaspase form and directly activates Caspase-3 and other caspases in the cascade. These effector caspases then carry out cell death. Caspase-8 can also cause apoptosome formation and cytrochrome c release by cleaving a proapoptotic member of the Bcl-2 family, Bid. Effector caspases (Caspase-3, -6 and -7) are activated by both the intrinsic and extrinsic pathways, and are responsible for the dismantling of various cell structures by cleaving specific substrate, such as PARP and kinase MST1.
Outside of involvement with apoptosis, a subset of caspases, including Caspase-1, -4, and -5 in humans (Caspase-1 and -12 in mice), are known as inflammatory caspases and are involved in cytokine maturation. They are activated by multiprotein complex inflammasomes, and are initiator caspases with Caspase Activation Recruitment Domains at the N-terminus. While no specific substrates for human Caspase-4 or -5 have yet been identified, two human Caspase-1 substrates have been discovered, proIL-1ß and proIL-18. These cytokines are vital participants in inflammation, and have multiple functions. Some of proIL-18's functions are to induce adhesion molecule upregulation, activation of natural killer cell activity, and pro-inflammatory cytokines. IL-1ß is responsible for initiating and increasing many of the effects of host response and immunity to tissue damage and microbial invasion, and it is a major inflammation mediator.
GeneCards: The Human Gene Compendium. Aliases and Descriptions for CASP3 gene. "Caspase 3, apoptosis-related cysteine peptidase." Weizmann Institute of Science.
RefSeq. NCBI Gene Summary. "CASP1 caspase, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) [Homo sapiens]." NCBI, NIH.
Shi, Yigong. "Activation of Initiator Caspases: History, Hypotheses, and Perspectives," Journal of Cancer Molecules 1(1): 9-18, 2005.
D'Amelio, M. et. al. "Neuronal capase-3 signaling: not only cell death," Cell Death and Differentiation (2010) 17, 1104-1114, 2010.
Los, Marek (MD.) and Henning Walczak. Caspases: Their Role in Cell Death and Cell Survival. Molecular Biology Intelligence Unit, Springer, p. 74. 2003.
Martinon, F. and J. Tschopp. "Inflammatory caspases and inflammasomes: master switches of inflammation," Cell Death and Differentiation (2007) 14, 10-22, 2007.