在对细胞质DNA的反应中,AIM2激活了炎细胞和细胞死亡
Teresa Fernandes-Alnemri1, Je-Wook Yu, Pinaki Datta
1Department of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Nature
|January 23, 2009
概括
在黑色素瘤2 (AIM2) 中缺席的炎症酶体感知细胞质DNA,激活caspase-1和pyroptosis. 这一发现揭示了AIM2的存在.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 来自宿主或病原体的细胞质双链DNA激活了炎症体.
- 炎症酶激活导致caspase-1激活和亲介质素-1β成熟.
- 在炎症酶激活中,细胞质DNA的特定传感器仍然未被确定.
研究的目的:
- 为了确定负责细胞质DNA触发的炎症酶激活的传感器蛋白质.
- 阐明细胞质DNA激活炎症体的机制.
- 描述AIM2在炎细胞和炎细胞形成中的作用.
主要方法:
- 利用短干扰RNA (siRNA) 来击败巨细胞中的AIM2表达.
- 评估了对细胞质DNA的反应中的炎酶和热酶激活.
- 在一个不响应的细胞系 (HEK293T) 中表达AIM2,以测试诱导响应.
主要成果:
- 缺席的黑色素瘤2 (AIM2) 被确定为细胞质DNA传感器.
- AIM2的寡核酸/寡糖结合 (OB) 域感知着DNA,而它的pyrin域与ASC相互作用.
- AIM2的激活会导致ASC的pyroptosome形成,caspase-1的激活,以及pyroptotic细胞死亡.
结论:
- AIM2是检测细胞质DNA的炎症酶的关键组成部分.
- 细胞质DNA诱导了AIM2的寡合化,从而启动了炎症酶组合.
- AIM2-ASC相互作用触发了卡斯巴酶-1激活和热,这是关键的先天免疫反应.
相关概念视频
01:17The 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...
01:31The 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...
01:30Apoptosis
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.
01:24Caspases
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.
01:18Autophagic 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.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
01:30Overview 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...