通过直接激活caspase-3,RGD会诱导细胞亡
C D Buckley1, D Pilling, N V Henriquez
1Division of Immunity and Infection, MRC Centre for Immune Regulation, The University of Birmingham, UK.
Nature
|February 24, 1999
概括
具有氨酸-甘氨酸-酸盐 (RGD) 基因的合成直接通过激活pro-caspase-3来触发亡. 这种RGD-机制绕过了细胞聚类,为癌症和炎症治疗提供了新的见解.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 氨酸-甘氨酸-酸盐 (RGD) 基因对整合素-连接体相互作用至关重要,调解细胞粘附,迁移,生长和分化.
- 含有RGD的被广泛用于研究这些因特林介导的过程.
研究的目的:
- 调查RGD含有的直接亡效应,独立于因特林介导的细胞聚类.
- 阐明RGD类诱导亡的分子机制.
主要方法:
- 用RGD含有的来治疗MCF-7乳腺癌细胞.
- 对前-3激酶激活和处理的分析.
- 在caspase-3缺乏细胞中评估RGD介导的细胞死亡.
主要成果:
- 含有RGD的直接诱导细胞亡,而不需要整合素介导的细胞聚类.
- 这些进入细胞并直接激活pro-caspase-3,这是一个关键的pro-apoptotic蛋白.
- 卡斯帕酶-3对于RGD介导的细胞死亡至关重要,正如在MCF-7细胞中证实的那样,卡斯帕酶-3基因被删除.
结论:
- 通过直接激活pro-caspase-3,可能通过pro-caspase-3内的RGD-DDM相互作用来诱导RGD.
- 这种机制为各种疾病模型中RGD的亲亡效应提供了另一种解释.
- 研究结果表明,针对血管新生,炎症和癌症转移中的亡的新型治疗策略.
相关概念视频
Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
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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
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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.
Autophagic Cell Death
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
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Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
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