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Immunomodulatory Activities of Silver Nanoparticles (AgNPs) in Human Neutrophils
Published in Huiliang Cao, Silver Nanoparticles for Antibacterial Devices, 2017
Apoptosis is a highly regulated process that could be triggered through either the extrinsic pathway, the intrinsic pathway or the endoplasmic reticulum (ER) stress-induced pathway (Bettigole and Glimcher 2015; Boyce and Yuan 2006; Roy et al. 2014). The intrinsic pathway is initiated through the intracellular release of different mitochondrial signal factors. In brief, after its release, cytochrome c will form a complex with adenosine triphosphate (ATP) and the enzymatic protein Apaf-1. This complex will in turn activate the initiator caspase-9 that will interact with the complex cytochrome c–ATP–Apaf-1, forming an apoptosome, leading to activation of the effector caspase-3 and degradation of cellular structures, including the cytoskeleton (Robertson et al. 2002; Roy et al. 2014). The extrinsic pathway is rather initiated via the stimulation of the transmembrane death receptors, including Fas receptors (CD95), one of the best characterised ones (Lavrik 2014). During activation of this pathway, some ligand molecules will be released by other cells and will bind to transmembrane death receptors on the target cell, inducing apoptosis. For example, the binding of the Fas ligands (CD95L) to their receptors (CD95) will trigger cell surface receptor aggregation, leading to the recruitment of an intracellular adaptor protein, Fas-associated death domain protein or FADD, which, in turn, will interact with the initiator caspase-8 protein, forming a complex, the death-inducing signal complex or DISC (Ashkenazi and Dixit 1998; Lavrik 2014; Li et al. 1998). Then, activated caspase-8 could activate caspase-3, indicating that both intrinsic and intrinsic pathway can overlap. In this respect, activated caspase-8 can also activate a protein, BID, known to act as a signal on the membrane of mitochondria facilitating cytochrome c release.
Monitoring Apoptosis and Anticancer Drug Activity in Single Cells Using Nanosensors
Published in Tuan Vo-Dinh, Nanotechnology in Biology and Medicine, 2017
In a study by Vo-Dinh and coworkers, a unique enzyme substrate–based optical nanobiosensor that consists of an enzyme substrate chemically immobilized to a nanotip was used to detect and identify surface-dependent cleavage events of caspase-9 in single live MCF-7 cells [35]. In this work, the application and utility of a unique optical nanobiosensor for monitoring the onset of the mitochondrial pathway of apoptosis within single living cell by detecting enzymatic activities of caspase-9 was demonstrated. The modified sensing format consists of a solid phase for the immobilization of caspase-9 substrate, leucine–glutamic acid–histidine–aspartic acid–7-amino-4-methyl coumarin (LEHD–AMC), which consists of a tetrapeptide, LEHD, coupled to a fluorescent molecule, AMC. LEHD–AMC exists as a nonfluorescent substrate prior to cleavage by caspase-9; however, after cleavage, free AMC fluoresces when excited at 325 nm. Caspase-9 is one of the most important Cysteinyl ASPartate-specific proteASE (caspase) among the caspase family members. It is synthesized as inactive proenzyme that is processed and activated in cells undergoing apoptosis. The processed form consists of large (35 kDa) and small (11 kDa) subunits, respectively, and antibody can be used to detect the 35 kDa protein corresponding to the large subunit to determine whether the cleavage of the inactive proenzyme occurred. Caspase-9 is thought to trigger a caspase-cascade leading to apoptosis [11]. As a result of mitochondrial membrane permeabilization by stimuli such as ROS, which may set the point-of-no-return of the PCD process [36,37], caspase activators, including cytochrome c and caspase-9, are released from the mitochondria intermembrane space into the cytosol. Cytochrome c release triggers the assembly of the cytochrome c/Apaf-A/pro-caspase-9 activation complex, the apoptosome, followed by the processing of caspase-9 [10,38].
Static electric field exposure decreases white blood cell count in peripheral blood through activating hypothalamic–pituitary–adrenal axis
Published in International Journal of Environmental Health Research, 2022
Jiahong Wu, Li Dong, Junli Xiang, Guoqing Di
As mentioned above, the elevation of CORT levels in peripheral blood could raise the concentration of CORT-GR complex in lymphocytes. Bim, a pro-apoptotic protein, is another target gene regulated by the CORT-GR complex (Wang et al. 2003; Dong et al. 2015; Dong and Vaux 2020). Bim can activate downstream pro-apoptotic proteins, especially Bax (Dong et al. 2015). Activated Bax could translocate from cytoplasm to outer mitochondrial membrane (OMM) and mediate the formation of permeability pores on OMM (Banuelos et al. 2016). After the permeability of OMM increases, cytochrome c, located between OMM and inner mitochondrial membrane, is released into the cytoplasm (Distelhorst 2002). In the cytoplasm, cytochrome c forms the apoptosome together with pro-caspase-9 and Apaf. The apoptosome could further activate caspase-3, which ultimately cleaves the majority of intracellular proteins to execute irreversible apoptosis (Smith and Cidlowski 2010). Therefore, the additional reason for the significant decrease of total WBC count and lymphocyte count in this study is that a SEF exposure of 7d and 14d can activate HPA axis. CORT, the end-product of HPA axis, induces the apoptosis of lymphocytes by upregulating Bim gene expression. To present the process in which the SEF exposure of 7d and 14d induce the apoptosis of lymphocytes more clearly, the discussion above is visually summarized in Figure 4(b).
Synthesis, crystal structures and anti-cancer mechanism of Cu(II) complex derived from 2-acetylpyrazine thiosemicarbazone
Published in Journal of Coordination Chemistry, 2022
Yunyun Zheng, Bin Li, Yu Ai, Mengyao Chen, Xinhua Zheng, Jinxu Qi
Studies have shown that the mitochondrial membrane potential drops and Cyt C is released into the cytosol to induce cell apoptosis. Cyt C combines with apoptosis-related factor 1 (apaf-1) to form a polymer that promotes caspase-9 to combine with it and form apoptotic bodies. Caspase-9 is activated, which further activates other caspases, such as caspase-7, thus inducing apoptosis [51, 52]. Therefore, it is necessary to study the effect of the Cu(II) complex on the apoptosis of A549 cells. After being exposed to 2 μM of L4 and 4a for 24 h, the A549 cells were stained with Annexin V-FITC and propidium iodide (PI) and were analyzed using flow cytometry. After the A549 cells were exposed to 2 μΜ of L4 and 4a for 24 h, the apoptosis percentages were 8.49%, 12.6%, 67.1% and 37.3%, respectively, as shown in Figure 5.
Mechanisms underlying the healing potentials of the methanol extract of Chasmanthera dependens stem on indomethacin-induced gastric ulcer
Published in Egyptian Journal of Basic and Applied Sciences, 2021
Abiola Stephanie Tijani, Ebenezer Olatunde Farombi, Samuel Babafemi Olaleye
Apoptosis is a crucial process for maintaining cellular homeostasis and encompasses different cell proteases and response to various apoptotic signals. Cleavage and degradation of the proteases result in cell death. Activation of caspases has been documented as the key to the apoptotic process and triggers the cells to undergo apoptosis [52]. Mitochondrial apoptotic pathway is usually mediated by the release of cytochrome c resulting in a cascade of events that activate caspase-9 and subsequent activation of caspase-3, the downstream effector caspase. The increase in the levels of Cyt-c, CASP-9 and -3 in IND alone group in this present study may contribute to the delay in gastric ulcer healing by inducing apoptotic response via generation of ROS, altered transition potential and mitochondrial permeability [53] in the rats. This result is in accordance with the previous report [54]. Again, MECD stem and CIM reversed these increases significantly (p< 0.01). Furthermore, the antiapoptotic effect of MECD stem was verified by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay and the result showed that MECD reduced the number of the apoptotic nuclei in the treated groups better than cimetidine.