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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
通过细胞毒性T细胞衍生型B粒酶激活质蛋白酶CPP32的激活
A J Darmon1, D W Nicholson, R C Bleackley
1Department of Biochemistry, University of Alberta, Edmonton, Canada.
Nature
|October 5, 1995
概括
细胞毒性T淋巴细胞使用酶B杀死细胞,该酶B激活了CPP32. 这种蛋白酶启动了亡,揭示了细胞介导免疫和编程细胞死亡的关键步骤.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 细胞毒性T淋巴细胞 (CTL) 介导的细胞毒性对于防御病毒感染,瘤和自身免疫性疾病至关重要.
- CTLs通过分泌的粒酶诱导目标细胞亡,但确切的机制尚不清楚.
- 格兰酶B对于诱导亡至关重要,但其直接基质和激活途径尚不清楚.
研究的目的:
- 为了识别granzyme B的细胞内基质.
- 为了阐明CTL介导的亡的分子机制.
- 了解大酶B在编程细胞死亡中的作用.
主要方法:
- 试验室试验分析了大酶B的活性.
- 蛋白酶裂解测定. 蛋白酶裂解测定.
- 西方涂抹检测蛋白质激活.
主要成果:
- 格兰酶B直接分裂并激活CPP32,这是一个关键的蛋白酶前体.
- 已激活的CPP32负责聚酸酶 (PARP) 的分裂.
- 这种分裂级联对于启动目标细胞中的DNA分裂和亡至关重要.
结论:
- 格兰酶B激活CPP32,这是一个在亡途径中的关键执行者蛋白酶.
- 大酶B-CPP32-PARP轴代表了CTL诱导细胞死亡的中心机制.
- 了解这种途径是调节免疫反应和治疗涉及CTLs的疾病的关键.
相关概念视频
Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...

