China
Africa
Explore chapters and articles related to this topic
Autoimmune Lymphoproliferative Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
The intracellular domain encoded by exon 9 is known as the death domain, which interacts with its ligand to form a death-inducing signaling complex consisting of FADD, caspase-8, and caspase-10, and triggers downstream effector caspase cascade, resulting in apoptosis. In addition, FAS is also capable of activating NF-kappaβ, MAPK3/ERK1, and MAPK8/JNK, and transducing proliferating signals in normal diploid fibroblast and T cells [8].
Microalgae and Cyanobacteria as a Potential Source of Anticancer Compounds
Published in Gokare A. Ravishankar, Ranga Rao Ambati, Handbook of Algal Technologies and Phytochemicals, 2019
The PUA first described in marine diatoms were 2-trans,4-cis,7-cis-decatrienal, 2-trans,4-trans,7-cis-decatrienal and 2-trans,4-trans-decadienal (DD) and were shown to display antiproliferative and apoptotic effects against the human adenocarcinoma CaCo2 cell line (Miralto et al. 1999). Following this, the marine diatoms Skeletonema marinoi and Thalassiosira rotula were found to produce PUA other than DD, including 2-trans,4-trans-heptadienal (HD), 2-trans,4-trans-octadienal (OD) and 2-trans,4-trans,7-octatrienal (d’Ippolito et al. 2002a; 2002b). The PUA DD was shown to induce an apoptotic effect in both copepod and sea-urchin embryos (Romano 2003). Further research on similar effects on human cancerous cells has been reported. For instance, testing on three PUA showed that they exerted cytotoxic effect on both A549 lung cancer and COLO 205 colon cancer cell lines but not on BEAS-2B normal cells (Sansone et al. 2014). In addition, DD activated the death signaling pathway in the lung cancer cells, which involved Tumor Necrosis Factor Receptor 1 (TNFR1) and Fas associated death domain (FADD), leading to necroptosis via caspase-3 without activating the survival pathway receptor-interacting protein (RIP).
Apoptosis and Cell Death
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
In apoptosis signalling, receptor trimerization leads to recruitment of FADD (Fas-associated death domain), which binds the intracellular death domain (DD) portion of Fas, and procaspase 8 molecules bind to the death effector domain (DED) of FADD (Figure 6.2). Hence, procaspase 8 molecules are clustered and activated by autocleavage on a platform known as the death inducing signal complex (DISC). Trimerized receptors may also cluster into receptor microaggregates. In some cell types (type I cells), caspase 8 activation at the DISC is sufficient for downstream effector procaspase cleavage, but in many cell types (type II cells), the mitochondrial pathway is engaged to amplify the death signal by caspase 8-dependent cleavage of the BH3-only protein Bid, converting it to a form that is able to transmit the apoptotic signal to the mitochondrion. In addition, cytotoxic T cells release perforin, which penetrates the epithelial cell membrane, and granzyme B, a serine protease that can cleave and activate Bid, hence engaging the mitochondrial pathway.
Potentiality of raloxifene loaded melittin functionalized lipidic nanovesicles against pancreatic cancer cells
Published in Drug Delivery, 2022
Usama A. Fahmy, Shaimaa M. Badr-Eldin, Hibah M. Aldawsari, Nabil A. Alhakamy, Osama A. A. Ahmed, Mohamed F. Radwan, Basma G. Eid, Shaban R. M. Sayed, Gamal A. El Sherbiny, Walaa Abualsunun
Additionally, it has been found that pro-apoptotic proteins such as Bax and pro-inflammatory cytokine TNF-α alter the MMP and alter the permeability transition pore (PTP) responsible for the release of cytochrome c from the outer mitochondrial membrane (Burke, 2017; Iqubal et al., 2019). Once cytochrome c is released from the mitochondrial pore, it associates with Apaf-1 and cascade for apoptosome formation, and caspases such as caspase 3 continues and results in apoptosis (Burke, 2017). Additionally, TNF-α binds with the TNF-α receptors and initiates the mechanism of extrinsic apoptosis via TNF receptor-associated death domain (TRADD) death-inducing signaling complex (DISC). In brief, binding of TNF-α with TNF-α receptor causes activation of procaspase-8 to caspase-8 that in turn convert procaspase-3 produced via Cyt c, Apaf-1, and apoptosome into caspase-3 and hence causes apoptosis (Josephs et al., 2018; Kretz et al., 2018). In the present study, exposure RLX-PL-MEL to the PANC1 cells showed reduced MMP, increased expression of TNF-α and caspase-3 and hence, signifies mitochondrial-mediated apoptosis. It is well established that the apoptotic potency of a drug candidate is validated by the success of an anticancer drug to arrest cycle. In the present study, using RLX-PL-MEL showed cell cycle arrest at the G2-M phase and confirmed the anticancer potential.
Primary Immunodeficiency and Thrombocytopenia
Published in International Reviews of Immunology, 2022
Maryam Mohtashami, Azadehsadat Razavi, Hassan Abolhassani, Asghar Aghamohammadi, Reza Yazdani
Some immune deficiencies are closely related to decrease platelet generation in this category. For example, FOXP3 gene disruption in T- cell signaling pathway causes immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, which affects T- cells regulatory function [267]. This gene has important roles in immune regulation. It has been demonstrated that PRKCD and IPEX deficiency not only decrease platelet activation, but also reduces platelet production derived from megakaryocytes, which ultimately lead to thrombocytopenia [268–272]. Additionally, the ALPS-FASLG signaling pathway, as the first one deficiency, describes a condition that autoimmune lymph proliferative syndrome (ALPS) result from FASLG deficiency [273]. The majority effect of FAS-associated death domain (FADD) deficiency on T and B cells is stimulated by apoptosis via FAS molecule. Furthermore, FADD is accompanied by proliferative responses in B cells via TLR3- and TLR4 [274]. On the other hand, the interaction between Caspases 8, 10 and FAS-associated protein with the death domain of FAS has an essential function in platelet production. Despite regulating the apoptosis pathway, previous studies have demonstrated that FAS and FAS-associated proteins with the death domain are capable to induce necrosis when caspases inhibit. Thus, in ALPS and FADD deficiency, caspase-8 and caspase 10 absence or reduction of caspases can lead to necrosis in megakaryocytes, consequently, platelet count decreased [275–277].
Extracellular vesicles of Fusobacterium nucleatum compromise intestinal barrier through targeting RIPK1-mediated cell death pathway
Published in Gut Microbes, 2021
Le Liu, Liping Liang, Chenghai Yang, Youlian Zhou, Ye Chen
To mimic the physiological conditions in vitro, we established a co-culture system of Caco-2 cells and macrophages to further investigate the specific function of FnEVs on epithelial integrity and permeability. We found that the apoptosis of Caco-2 cells and the damage to barrier function were significantly increased in the FnEVs-treated co-culture group, which indicated that apart from PCD of IECs, FnEVs augmented TNF-α induced PCD and increased epithelial permeability by creating a pro-apoptotic environment (Figure 2). Recent genetic and biochemical evidence suggests that upregulated RIPK1 signaling can induce caspase-independent apoptosis.13,14,41 RIP1 was initially discovered as an interaction partner for the first apoptosis signal receptor (Fas). The RIP1 death domain (DD) is necessary for interaction with other death receptor proteins, such as TNFR1, TRAILR1, TRAILR2, and other DD-containing adaptor proteins like TRADD and FADD.42 Nec-1 is a specific phosphorylated RIPK1 kinase inhibitor that blocks RIPK1-mediated cell death. To elucidate the exact mechanism of apoptosis induced by FnEVs, we employed TNF-α neutralizing antibody and Nec-1 against RIPK1 and its downstream factors. We found that both of these could inhibit the activation of RIPK1 in FnEVs treated PBMC/Caco-2 co-culture systems. Besides, increased permeability of the epithelial barrier and over-activated caspase-3 were also reversed by application of TNF-α neutralizing antibody and Nec-1 (Figure 3). This confirmed the involvement of the RIPK1-mediated caspase-3 signaling pathway in UC pathogenesis induced by microorganisms.