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The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
An effective mechanism is required to remove cells that are damaged or no longer necessary. This programmed cell death is generally known as apoptosis (Figure 2.7), and follows a carefully controlled series of events allowing the cell to condense its cytoskeleton and fragment its DNA. Apoptosis is driven by members of the caspase protein family. Bcl proteins regulate caspase activity. Programmed cell death can be triggered in response to stimuli such as cell surface signals or mitochondrial stress. Following ligand binding, cell-surface death receptors such as Fas recruit adaptor proteins to trigger procaspase activation, and thus elicit apoptosis. Mitochondria can initiate an alternative apoptotic pathway in response to DNA damage or intracellular oxidative stress. A dying cell will show membrane blebbing, cell shrinkage and protein fragmentation as it collapses in upon itself. Within the nucleus, chromatin condensation and DNA degradation occur. Finally, the cell is flagged for uptake by phagocytic cells.
Chemopreventive Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
At present there are many in vitro and in vivo studies underway to further investigate the cancer chemoprotective effects of NSAIDs. For example, in 2018 it was reported that sulindac is a potent inducer of apoptosis in MCF‑7 breast tumor cells in a dose‑dependent, and time-dependent manner. An accompanying western blot analysis demonstrated that protein expression of Bcl‑2 was down-regulated, and Bax and cleaved caspase‑3 were up-regulated. There are likely to be many further studies of this type in the future to fully explore the cancer chemopreventive potential of the large number of NSAIDs available.
Testicular germ cell apoptosis and spermatogenesis
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Caspases are the initiators and executioners of apoptosis. They are synthesized in the form of procaspases, which get activated during the apoptotic process (73). These procaspases contain three domains: an NH2 domain and the p20 and p10 domains. Caspases are cysteine proteases that cleave their substrate protein after the aspartic acid residue that leads to cell death (45). The executioner caspases exist in the cytosol in the form of inactive dimers, and their activation is carried out by the initiator caspases through proteolytic cleavage of its catalytic domain to an active scaffold. The proteolytic cleavage allows the rearrangement of its mobile loop conferring it the catalytic activity (74,75). In the cytosol, caspase-3 and caspase-7 exist in their dimeric forms, and activation is through the cleavage within their respective linker segments (76). In human testis biopsies, effector caspase-7 seemed to be absent from normal human testes, whereas procaspase-3 and procaspase-6 were detected in germ cells. Increased germ cell apoptosis in patients with the spermatogenic arrest was associated with increased levels of active caspase-3, which indicates that caspase-3 is the major executioner of apoptosis in human infertility (77). Similarly, in rodents also caspase-3 appears to be the major executioner of apoptosis (78,79).
Melatonin pretreatment can improve the therapeutic effect of adipose-derived stem cells on CCl4-induced liver fibrosis
Published in Toxin Reviews, 2023
Ziqiang Zhang, Yingying Sun, Haojie Wang, Yuxiang Yang, Ruiqi Dong, Yaolu Xu, Mengyu Zhang, Qiongxia Lv, Xiaoguang Chen, Yumei Liu
The Bcl-2 and Caspase families play an indispensable role in the execution and regulation of apoptosis. The expression levels of the proteases caspase-8, Bax, and caspase-3; the antiapoptotic gene Bcl-2; and the proapoptotic gene Bax in each group were detected via qPCR. As shown in Figure 4, compared with the control group, the expression levels of Bcl-2 were significantly reduced and the expression levels of Caspase-8, Bax, and Caspase-3 were significantly increased in the model group (p<0.01). After treatment with ADSCs, the expression level of Bcl-2 was significantly increased (p<0.01), and the expression levels of Caspase-8, Bax, and Caspase-3 were significantly decreased (p<0.01). Notably, the changes in the ADSC + Mel group were more significant. The above results indicate that Mel-incubated ADSCs had a better therapeutic effect on CCl4-induced hepatocyte apoptosis.
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.
Edible Tuber Amorphophallus paeoniifolius (Dennst.) Extract Induces Apoptosis and Suppresses Migration of Breast Cancer Cells
Published in Nutrition and Cancer, 2021
Munmi Majumder, Manoj Sharma, Siddhartha Maiti, Rupak Mukhopadhyay
Induction of apoptosis is a possible mode of cell death in cancer cells. Treatment of APTE induced significant apoptosis in both MCF-7 and MDA-MB-231 cells. Dose-dependent increase of pro-apoptotic BAX and inhibition of antiapoptotic BCL-2 indicated induction of apoptosis by the extract. BAX is a key component for apoptosis via mitochondrial stress and increases membrane’s permeability. This results in the release of cytochrome c from mitochondria and initiation of CASPASE activation pathway for apoptosis. There are reports that demonsrtrate p53-mediated induction of BAX. However, APTE treatment did not induce p53 expression suggesting BAX activation in this case might be independent of p53 (35). The expression of CASPASE-7 is a major contributor to the execution of apoptosis. It is cleaved by different enzymes whose expressions are upregulated during apoptosis. The activated CASPASE-7 is responsible for cleavage of many substrates, including PARP. APTE successfully induced CASPASE-7 activation leading to cleavage of PARP in experimental cells (36). These observations suggest that APTE induces apoptosis in both MCF-7 and MDA-MB-231 cells possibly by a CASPASE-7 dependent pathway (37).