Imaging Cellular Networks and Protein-Protein Interactions In Vivo
Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman in Molecular Imaging in Oncology, 2008
The cysteine protease caspase-3 is an effector caspase activated during apoptotic cell death by upstream initiator caspases (i.e., caspases 8, 9, 10, and 12). Once activated, caspase-3 executes apoptosis by cleaving cellular proteins at a specific DEVD consensus motif. To enable noninvasive and repetitive imaging of apoptosis in living animals, a reporter was engineered (34) for bioluminescence imaging wherein the estrogen receptor regulatory domain was fused to FLuc, thereby sterically silencing FLuc catalytic activity. Inclusion of a DEVD sequence between these two moieties allowed for caspase-3-mediated restoration of luciferase activity, enabling real-time monitoring of apoptotic activation. Using this reporter, the investigators demonstrated activation of caspase-3 in intact cells and living animals in response to treatment with TNF-α-related apoptosis-inducing ligand (TRAIL). Furthermore, ZVAD-fmk, a general caspase inhibitor, was shown to abrogate TRAIL-induced reporter activation, thus confirming the role of caspases for regulating activity of this reporter.
Tissue Staining Techniques for Stroke Studies
Yanlin Wang-Fischer in Manual of Stroke Models in Rats, 2008
We abstracted some information about caspase-3 from the Chemicon Web site (with permission) to help investigators better understand the method. Caspase-3 (CPP32, Apopain) is the most extensively studied apoptotic protein. Caspase-3 is synthesized as an inactive proenzyme (32 kDa) that is processed in cells undergoing apoptosis by self-proteolysis and/or cleavage by another upstream protease. The processed form of caspase-3 consists of large (17 kDa) and small (12 kDa) subunits which associate to form an active enzyme. The active caspase-3 proteolytically cleaves and activates other caspases, as well as relevant targets in the cells such as PARP and DFF. AB3623 detects only the cleaved p17 fragment and does not detect the precursor form in cells undergoing apoptosis.
The role of apoptosis in non-mammalian host-parasite relationships
G. F. Wiegertjes, G. Flik in Host-Parasite Interactions, 2004
Caspases (cysteine aspartate-specific proteases; Alnemri et al., 1996) are present in inactive pro-enzyme form in nucleated cells and are generally activated by cleavage. They are site-specific proteases, which recognize sequences of three or four amino acids, always ending in aspartate. In this way, rather than causing indiscriminate degradation of cellular proteins, caspases act on particular targets to cause the biochemical and morphological changes characteristic of apoptosis. The cleavage of targets is effectively irreversible, as is appropriate for the elimination of unwanted or potentially harmful cells. Some of the most important targets for caspases are other caspases, so that the response is amplified in a cascade and thus shows some similarities to complement activation or blood-clotting. Caspase 3, for example, is activated during apoptosis by upstream caspases in response to many different stimuli, whereas other caspases, acting upstream in particular signalling pathways, act to initiate the cascade.
Hybrid nanocarrier system for guiding and augmenting simvastatin cytotoxic activity against prostate cancer
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Mohammed Sedki, Islam A. Khalil, Ibrahim M. El-Sherbiny
Caspase-3 is one of protease family enzymes which play essential roles in programmed cell death. It is mainly activated during the early stages of apoptosis where it is synthesized as an inactive pro-enzyme then undergoes activation during apoptosis cascade. Treatment of PC-3 cells with SMV and F (1:4) NPs significantly increased the level of active caspase-3 compared to control untreated cells (Figure 5(i)). The up-regulation of the Caspase 3 confirms results of both cell cycle study and annexin V/Propidium iodide apoptosis assay. All of these findings were in alignment with the published report on statins as potential anticancer agents. [53] In this report several mechanisms were discussed specially the effect of statins on proapoptotic phase where activation of caspase-3 and retardation of G2-M phase were highlighted.
Protective effect of hyperoside against hydrogen peroxide-induced dysfunction and oxidative stress in osteoblastic MC3T3-E1 cells
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
Xin-Chun Qi, Bo Li, Wen-Liang Wu, Hai-Chun Liu, Yun-Peng Jiang
In this study, after treatment with H2O2, Bax, caspase-3 and caspase-9 were significantly increased, which indicated that H2O2 could increase the apoptosis rates. And Bcl-2 significantly decreased after H2O2 treatment compared with the negative control. When co-cultured with HYP, the Bcl-2 expression was significantly increased, which indicated that HYP could protect the MC3T3-E1 cells against the apoptosis induced by H2O2. Caspase-3 is cleaved and activated in the process of apoptosis. HYP significantly inhibited the caspas-3 expression induced by H2O2 in MC3T3-E1 cells, which demonstrated the anti-apoptotic effect of HYP on oxidative stress-induced MC3T3-E1 cells apoptosis.
Design, synthesis, apoptotic, and antiproliferative effects of 5-chloro-3- (2-methoxyvinyl)-indole-2-carboxamides and pyrido[3,4-b]indol-1-ones as potent EGFRWT/EGFRT790M inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Lamya H. Al-Wahaibi, Anber F. Mohammed, Fatema El-Zahraa S. Abdel Rahman, Mostafa H. Abdelrahman, Xuyuan Gu, Laurent Trembleau, Bahaa G. M. Youssif
Caspases have an important role in the induction and completion of apoptosis33. Among caspases, caspase-3 is an important caspase that cleaves various proteins in cells, resulting to apoptosis34. Compounds 5f and 5 g, the most potent derivatives, were tested as caspase-3 activators against pancreatic cancer cell line (Panc-1)32, and the results are shown in Table 3. Compounds 5f and 5 g demonstrated excellent caspase-3 protein overexpression levels of 560.2 ± 5.0 and 542.5 ± 5.0 pg/mL, respectively. They increased the protein caspase-3 in the Panc-1 human pancreatic cancer cell line by approximately 8 times when compared to control untreated cells, and they were even more active than the reference staurosporine (503.2 ± 4.0 pg/mL). These results indicate that the tested compounds act as caspase-3 activators and can therefore be regarded as apoptotic inducer agents.
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