The Role of Nanoparticles in Cancer Therapy through Apoptosis Induction
Hala Gali-Muhtasib, Racha Chouaib in Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Apoptosis is an energy-dependent process. Two main apoptotic signaling pathways, including the extrinsic death receptor pathway and the intrinsic mitochondrial pathway, have been well-characterized. However, there are additional pathways that involve the T-cell-mediated cytotoxicity and the perforin-granzyme pathway. The perforin/granzyme pathway induces apoptosis through either granzyme B or granzyme A. Another recent pathway of apoptosis is mediated by the endoplasmic reticulum (ER) which plays important roles in cell fate and will be discussed in details later [17]. Apoptosis is mediated by chronological activation of protein superfamily of caspases [16]. Caspases are expressed in an inactive form of proenzymes in most cells. When activated, they activate other procaspases, leading to the initiation of the cascade of caspase-dependent apoptosis pathway. Caspases are highly conserved cysteine-dependent aspartate-specific proteases. There are different types of caspases: initiator caspases, including CASP-2, 8, 9, and 10; effector caspases, such as CASP-3, 6, and 7; and inflammatory caspases which are CASP-1, 4, and 5). The other caspases that have been recently studied are (i) caspase-11, which is involved in the regulation of apoptosis and cytokine maturation during septic shock, (ii) caspase-12, which mediates apoptosis through the endoplasmic reticulum, (iii) caspase-13, which is believed to be a bovine gene, and (iv) caspase-14, which is highly expressed just in embryonic tissues [23]. Initiator caspases are inactive until specific oligomeric activator protein binds to them. Subsequently, they bind to effector caspases. Effector caspases are then activated through proteolytic cleavage. The activated caspases then proteolytically degrade the intracellular proteins necessary for programmed cell death.
Curcumin inhibits cerebral ischaemia–reperfusion injury and cell apoptosis in rats through the ERK–CHOP–caspase-11 pathway
Published in Pharmaceutical Biology, 2022
Yue Chen, Lixia Zhang, Zengtai Yang, Jie Yu
Caspase-11 is a protein with a dual role that can cause apoptosis and inflammation (Vanaja et al. 2016; Lu et al. 2019). CHOP, also known as growth arrest and DNA damage-inducing gene 153, is one of the transcription factors of endoplasmic reticulum stress, which can cause cell apoptosis. Cerebral ischaemia and reperfusion cause abnormal endoplasmic reticulum stress response and inhibit the expression of CHOP (Lv et al. 2018; Song and Ping 2018). Meanwhile, it will activate the related signal pathway of inflammatory response, leading to the overexpression of inflammatory factor IL-1β (Lv et al. 2018; Song and Ping 2018). Consistently, this study found that after curcumin administration, the protein and mRNA expression of caspase-11 and CHOP increased, while the expression of the inflammatory factor IL-1β decreased, suggesting that curcumin may inhibit apoptosis and inflammation via caspase-11 and CHOP. ERK1/2 is one of the important members of the MAPK family. The ERK1/2 signal transduction pathway can promote cell proliferation and differentiation, inhibit apoptosis and reduce tissue inflammation after being activated by external stimuli. ERK activated by phosphorylation can prevent nerve functional defects and neuronal death and have a protective effect on cerebral ischaemia and reperfusion (Feng and Hu 2018; Yuan et al. 2018; Zhao et al. 2018). Similarly, we showed that the protein level of p-ERK in the brain tissue of rats increased significantly after curcumin administration, indicating that curcumin may exert its effects through regulating ERK.
Latent Upregulation of Nlrp3, Nlrc4 and Aim2 Differentiates between Asymptomatic and Symptomatic Trichomonas vaginalis Infection
Published in Immunological Investigations, 2022
Sonal Yadav, Vivek Verma, Rakesh Singh Dhanda, Sumeeta Khurana, Manisha Yadav
Gene CASPASE-4 is an apoptosis-related cysteine peptidase, and its encoded protein has historically been called caspase 11. Recently studies reported IL-1β cleavage and secretion by caspase 11 in the mice and caspase 4/5 in humans due to LPS interaction; this mechanism is non-canonical inflammasomes activation (Knodler et al. 2014). High expression of CASPASE-4 was observed in vaginal tissues of the symptomatic group on the 8th dpi and on (4th dpi and 14th dpi) in the asymptomatic group as compared to the control group. In vaginal tissues of the asymptomatic group, significant levels of CASPASE-4 was measured on the 4th dpi as compared to the 2nd dpi, but no significant difference was observed between the symptomatic and asymptomatic groups (Figure 6c). In the cervical tissue of the symptomatic group, a high CASPASE-4 level was measured on the 4th dpi and 8th dpi as compared to the control.
Disulfiram ameliorates ischemia/reperfusion-induced acute kidney injury by suppressing the caspase-11-GSDMD pathway
Published in Renal Failure, 2022
Qiaoting Cai, Zhaoxing Sun, Sujuan Xu, Xiaoyan Jiao, Shulan Guo, Yingxiang Li, Huan Wu, Xiaofang Yu
GSDMD is one of the effector proteins of pyroptosis. To date, two mechanisms explain the interpretation of GSDMD membrane pore formation and the inflammatory response [24,25]. One is the classical pathway, which is the typical NLRP3 inflammasome pathway. The NLRP3 inflammasome can recognize diverse DAMPs and pathogen-associated molecular patterns (PAMPs) and bind to pro-caspase-1 through ASC; then, caspase-1 is generated by the cleavage of pro-caspase-1, which results in the maturation of IL-1β and IL-18 [26,27]. The other pathway is the nonclassical inflammasome pathway, in which PAMPs (such as LPS) activate caspase-11 (human caspase-4 and caspase-5) directly or through TLR4 [24]. In our study, we confirmed the activation of these two inflammasome pathways in a kidney IR injury model. However, there were some specific circumstances in our experiment. After disulfiram treatment, we confirmed that caspase-1, GSDMD and mature IL-1β and IL-18 were significantly decreased, but the expression of ASC and NLRP3 did not change significantly after drug administration. We hypothesized that the downregulation of caspase-1 expression was incidental to the reduction in caspase-11 since caspase-11 was also involved in the regulation of caspase-1 formation [28–30].
Related Knowledge Centers
- Caspase 4
- Inflammasome
- Innate Immune System
- Lipopolysaccharide
- Protease
- Cytosol
- Caspase 5
- Toll-Like Receptor 4
- Toll-Like Receptor 3
- Ticam1