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Introduction to Cancer, Conventional Therapies, and Bionano-Based Advanced Anticancer Strategies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Necrosis is a death mechanism, in which cells die accidently in response to an acute insult such as snake biting, trauma or lack of blood supply, etc. In the case of necrosis, the cells undergo plasma membrane permeabilization, swelling, and rupture, and by that the necrotic cells spill out the cellular contents over their neighbors, which invite the damage associated molecular patterns (DAMPs) and may initiate inflammation. Necrosis is also termed as necroptosis and it is mediated by death receptor TNFR1 (tumor necrosis factor receptor). On TNF stimulation, TNFR1 goes through a confirmation change and recruits TNFR-associated death domain protein (TRADD), TRARF2, cellular inhibitor of apoptosis protein 1 (cIAP1), cIAP2, and receptor interacting protein kinase 1 (RIPK1), to form complex 1. RIPK1 is polyubiquinated by cIPA1 and c1PA2 activates NFkB. Caspase 8 cleavage induces apoptosis, in certain condition, and caspase 8 inhibition will induce necroptosis. Necroptosis involves several factors such as ROS production, lysosomal permeabalization, AIF release, and PARP activation. When caspase activation is not involved, necroptosis is associated with the formation of autophagic vesicles.
Apoptosis of Biliary Epithelial Cells
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Natalie J. Török, Gregory J. Gores
Caspase 8 is the initiator caspase in the death-receptor pathway. After the ligands bind to the death receptors such as CD95 (Apol-Fas), TNF-α (TNF-α receptor) or TRAIL-ligand (TRAIL-receptor), aggregation, and formation of membrane-bound signaling complexes occur. These complexes then recruit several molecules of pro-caspase 8, and the resulting high concentration of the enzyme results in auto-activation.5 Once caspase 8 is activated, it cleaves cytosolic Bid, a proapoptotic Bcl-2 family member. The carboxyl fragment of Bid translocates to the mitochondria, where it induces cytochrome c release. Downstream effector caspases are then activated and cell death occurs. Caspase 8 may bypass the mitochondrial requirement in some cells such as lymphocytes,6 by direcdy cleaving caspase 3. Mitochondria, however, substantially amplify the caspase 8-induced cascade.
Cell-mediated immunity
Published in Gabriel Virella, Medical Immunology, 2019
José C. Crispín, Gabriel Virella
A second pathway through which CD8 T cells can induce apoptosis in target cells is mediated by membrane-bound molecules such as FasL. FasL binds to Fas (CD95) and promotes the assembly of a death-inducing signaling complex in the Fas-bearing cell. The activation of this pathway is associated with activation of caspase 8, which in turn will trigger the cascade that leads to activation of effector caspases and apoptosis. These two pathways are not mutually exclusive. In fact, there is data that suggest that activation of both pathways is required in vivo for efficient cytotoxicity.
Effects of radiofrequency radiation on apoptotic and antiapoptotic factors in colorectal cancer cells
Published in Electromagnetic Biology and Medicine, 2022
Sanem Gökçen, Berrak Kurt, Yusuf Küçükbağrıaçık, Elcin Ozgur-Buyukatalay, Görkem Kismali
The immune system destroys defective cells by apoptosis, but cancer cells can develop defense mechanisms by increasing resistance to apoptosis. Inducing apoptosis is a new therapeutic target for cancer cells (Bremer et al. 2006). Members of the BCL-2 family play an important role in deciding whether a cell will survive in the event of cellular damage. BCL-2 family members are anti-apoptotic proteins like BCL-2, BCL-XL, pro-apoptotic like BCL-W BAX, BAK, BCL-XS (Adams and Cory 2001; Gross et al. 1999). Survivin is a member of the inhibitor family of apoptosis proteins (IAP) and is often indicated in cancer cell lines. Members of the human IAP family proteins XIAP, c-IAP1 and c-IAP2 are involved in the inhibition of caspases 3, 7, and 9, while survivin is involved in the inhibition of caspase 3 and 7 (Suzuki et al. 2001). Caspase-8 plays a role in suppressing cellular necrosis and regulating auto-phage and increasing cellular adhesion. Defects in the role of caspase-8 can cause tumor development and progression (Graf et al. 2014).
The protective effect of fasudil against acrylamide-induced cytotoxicity in PC12 cells
Published in Drug and Chemical Toxicology, 2020
Mostafa Kianfar, Alireza Nezami, Soghra Mehri, Hossein Hosseinzadeh, A. Wallace Hayes, Gholamreza Karimi
Another major mechanism in ACR-induced neurotoxicity, which has been considered in several studies, is apoptosis. Bcl-2 is a family of regulator proteins which include pro-apoptotic or anti-apoptotic proteins that modulate apoptosis (Tsujimoto et al. 1984, Cleary et al. 1986). It seems that the main action of the Bcl-2 family of proteins is the regulation of cytochrome C release from the mitochondria through alteration of mitochondrial membrane permeability. Resistance to apoptosis can be by the up-regulation of anti-apoptotic proteins such as Bcl-2 or by the down-regulation of pro-apoptotic proteins such as Bax (Elmore 2007). For this reason the Bax/Bcl-2 ratio is an important predictor of apoptosis (Oltvai et al. 1993). Caspases also play an important role in apoptosis (Elmore 2007). Elevation of the Bax/Bcl-2 ratio results in release of cytochrome C, then cytochrome C can bind to Apaf-1 and form apoptosomes, thus activating caspase-9 which can directly activate caspase-3(Li et al. 1997, Srinivasula et al. 1998). Caspase-8, a cysteine protease, is important in the extrinsic apoptotic signaling pathway through death receptors. Activated caspase-8 regulates apoptosis either by directly cleaving and activating downstream caspases or by cleaving the BH3 Bcl2-interacting protein, which causes the release of cytochrome c from mitochondria (Kruidering and Evan 2000). Caspase-3 is an executioner caspase and its activation can cause degradation of chromosomal DNA, cytomorphological changes and formation of apoptotic bodies (Elmore 2007).
Direct Peritoneal Resuscitation Reduces Lung Injury and Caspase 8 Activity in Brain Death*
Published in Journal of Investigative Surgery, 2020
Jessica L. Weaver, Jessica E. Schucht, Paul J. Matheson, Amy J. Matheson, Cameron A. Ghazi, Cynthia D. Downard, Richard Neal Garrison, Jason W. Smith
Tissue injury can occur through a variety of different mechanisms. However several studies of acute lung injury from both hemorrhagic shock and sepsis propose that the initial apoptotic response may play a key role in the organ-specific inflammatory response. Apoptosis is frequently described as “programmed cell death,” and is an energy-dependent process that removes cell DNA, proteins, and organelles in an organized fashion with minimal damage to surrounding cells [14]. This requires the activation of caspase proteases [15] and can occur through two different pathways that trigger caspase activation. The extrinsic pathway is activated by an external signal binding to a receptor [14], and the intrinsic pathway that causes increased permeability of the mitochondrial membrane, and the release of cytochrome c and other pro-apoptotic molecules [16] in response to intracellular signals. Multiple studies have established that apoptosis is increased in many organs, including the liver, kidneys, and lungs after ABD [17, 18]. This leads to increased tissue injury and is associated with delayed graft function [18]. Caspase 8 is a cysteine protease that typically initiates apoptosis in response to signaling from “death receptors,” such as tumor necrosis factor (TNF) receptors [19].