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Autoimmune Lymphoproliferative Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
The pathogenesis of ALPS is largely attributed to defective apoptosis of lymphocytes mediated via the FAS/FASLG (FAS ligand) signaling pathway. As CASP10 participates in the formation of a death-inducing signaling complex composed of FADD, caspase-8, and caspase-10, which triggers the downstream effector caspase cascade of the FAS/FASLG signaling pathway, it may also impact on lymphocyte apoptosis [6,7].
Imaging of Cardiovascular Disease
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Aleksandra Kalinowska, Lawrence W. Dobrucki
Cell death can be initiated through two different mechanisms—the intrinsic and extrinsic pathways. The extrinsic pathway is started mainly through extracellular signals and targets cell membrane receptors like Fas, a common mammalian death receptor present in both humans and rodents. The intrinsic one is generated from within the cell through DNA damage, mitochondrial signals, and oncogene activation. Although initial triggers remain separate, upon the activation of a death-inducing signaling complex (DISC), the pathways have been proven to adopt the same effector caspase machinery, involving the activation of multiple caspase proteins (Blankenberg 2008). Molecular imaging takes advantage mainly of the extrinsic pathway as it involves cellmembrane components, such as phosphatidyl serine, which is present outside the cell during apoptosis and form suitable sites for the binding of imaging radiotracers. When cell disintegration progresses, cellular membranes lose potential, and intracellular structures dissipate, exposing proteins, such as histones and other organelle components, which have also been utilized for imaging techniques.
Other Novel Targeted Therapies in Lung Cancer
Published in Kishan J. Pandya, Julie R. Brahmer, Manuel Hidalgo, Lung Cancer, 2016
Kyriakos P. Papadopoulos, Anthony W. Tolcher
Caspase activation and execution in the common postmitochondrial apoptotic pathway is under regulatory control by inhibitor of apoptosis proteins (IAP), providing a further potential opportunity for intervention with targeted anticancer therapy (97). The IAP family members XIAP, cIAP1, and cIAP2 have characteristic baculovirus IAP repeat (BIR) and RING finger domains (98,99). The BIR domains of IAP interfere with processing and activation of caspase-9 and directly bind and inhibit activated terminal effector caspase-3 and -7. The RING domain mediates selective ubiquitination and degradation of IAP-caspase complexes, further abrogating apoptosis. Smac released from mitochondria with cytochrome c can bind and sequestrate IAP, allowing caspases to escape regulation and accomplish apoptosis. Overexpression of IAP is associated with resistance to chemotherapy and apoptosis; inhibiting IAP thus promotes caspase activation and tumor cell death.
B-Raf inhibitor vemurafenib counteracts sulfur mustard-induced epidermal impairment through MAPK/ERK signaling
Published in Drug and Chemical Toxicology, 2023
Zhiyong Xiao, Feng Liu, Junping Cheng, Ying Wang, Wenxia Zhou, Yongxiang Zhang
SM-induced apoptosis occurs via the intrinsic mitochondrial apoptosis pathway as well as the extrinsic death receptor (Fas) pathway (Rosenthal et al.1998, 2003). These two pathways are collectively involved in the activation of the effector caspase-3/7. In our study, exposure to 100 and 500 μM SM for 6 h led to an increase in caspase-3/7 activity in a concentration-dependent manner; this increase was more than 2.5-fold higher in the cells treated with 500 μM SM than in untreated cells (Figure 2(a)). Caspase-3/7 activity increased further after 24 h of 100 μM SM exposure, although it remained stable in cells treated with 500 μM SM (Figure 2(b)). Vemurafenib suppressed the SM-induced caspase-3/7 activation in HaCaT cells challenged with 100 μM SM, as their levels were constant after 6 and 24 h of SM exposure. This effect was also significant after 500 μM SM exposure at both time points (Figure 2(a,b)). SM-mediated apoptosis was also evident from the accumulation of living cells (PI staining negative) in the sub-G1 phase of the cell cycle after 24 h of SM exposure. This effect was inhibited by vemurafenib, which decreased the percentage of these cells, thus indicating an anti-apoptosis effect (Figure 2(c)).
Regulation of the autophagy plays an important role in acute kidney injury induced acute lung injury
Published in Renal Failure, 2022
Ruolin Wang, Siheng Shen, Luyong Jian, Shuhua Liu, Qi Yuan, Huahui Guo, Jiasheng Huang, Penghui Chen, Renfa Huang
Autophagy and apoptosis are two important cellular processes. In many other cases, autophagy and apoptosis develop exclusively. However, autophagy and apoptosis may be triggered by common upstream signals, and sometimes these results in combined autophagy and apoptosis. Apoptosis is a programmed cell death, and its initiation is dependent on the activation of a series of cysteine-aspartic proteases known as Caspases. There are two categories of Caspases, including initiator Caspase and effector Caspase. Caspase-3 is an effector Caspase. Active caspase-3 is responsible for the final execution of proteolytic degradation of a variety of intracellular proteins [39]. Members of the Bcl-2 protein family are responsible for the regulation of apoptosis and are critical to the regulation of both intrinsic and extrinsic apoptotic pathways [40]. As mentioned above, Bcl-2 can combine with Beclin-1 to participate in the process of apoptosis. When autophagy is promoted, the degree of apoptosis will be reduced accordingly. Our results showed that decreased Caspase-3, increased Bcl-2 and Beclin-1, represent the decreased apoptosis in lung and kidney tissues when autophagy was promoted. According to our results, we can speculate that autophagy not only plays a role in the lung-kidney crosstalk through anti-inflammatory and antioxidation, but also plays a protective role in the inhibition of apoptosis.
Synthetic pyrethroids common metabolite 3-phenoxybenzoic acid induces caspase-3 and Bcl-2 mediated apoptosis in human hepatocyte cells
Published in Drug and Chemical Toxicology, 2022
Dilek Guvenc, Sinem Inal, Nilufer Kuruca, Sedat Gokmen, Tolga Guvenc
In mammals, there are three major types of cell death, namely, apoptosis, autophagy and necrosis (Ou et al.2017). Apoptosis means programmed cell death triggered by various physiological and pathological situations. The mechanism of apoptosis can be triggered by both intrinsic and extrinsic signaling pathways. The extrinsic pathway, known as the receptor-mediated pathway, often plays a role in inflammatory responses and cellular homeostasis (Elmore 2007). The intrinsic pathway, also known as the mitochondrial pathway, is stimulated by tetrachlorodibenzo-p-dioxin, various heavy metals, pesticides and toxins (Roy and Nicholson 2000, Curtin and Cotter 2003). Fundamental roles in the activation of this pathway are played by caspases, namely caspase-9, caspase-7, caspase-6, and caspase-3, and the Bcl-2 protein family members, including Bcl-2, Bax, Bid, Bcl-XL, especially caspase-3 and Bcl-2 proteins. The Bcl-2 family proteins, which are located in the outer membrane of the mitochondria, endoplasmic reticulum and nuclear envelope, are potent anti-apoptotic proteins (Ola et al.2011). Caspase-3, which is recognized as the main effector caspase, is involved in both intrinsic and extrinsic apoptosis pathways, causing the fragmentation of DNA which leads to apoptosis (Riedl and Shi 2004).