在哺乳动物发育过程中,Apaf1 (CED-4同类) 调节了编程细胞死亡
F Cecconi1, G Alvarez-Bolado, B I Meyer
1Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Göttingen, Germany.
Cell
|September 30, 1998
概括
亡蛋白酶激活因子1 (Apaf1) 对哺乳动物发育至关重要. 它的缺失导致胚胎致死性和严重的发育缺陷,原因是受损的编程细胞死亡.
科学领域:
- 发育生物学 发展生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 细胞亡蛋白酶激活因子1 (Apaf1) 是内在细胞亡路径的关键组成部分.
- 它调解了卡斯帕酶9 (CASP9) 的激活,随后是卡斯帕酶3 (CASP3).
- Apaf1在哺乳动物胚胎发育和编程细胞死亡中的作用尚未完全理解.
研究的目的:
- 研究Apaf1在哺乳动物胚胎发育中的功能.
- 确定Apaf1在胚胎发生过程中被编程细胞死亡中的作用.
主要方法:
- 对于小鼠Apaf1.1.的基因陷零等位基因生成.
- 对同卵性Apaf1突变胚胎的表型分析.
- 在现场免疫检测卡斯帕酶3激活.
主要成果:
- 同性卵性Apaf1突变体在16.5日表现出胚胎致死性.
- 突变者表现出严重的面形,大脑过度生长,持续的数字间网络和眼睛异常.
- 缺少Apaf1导致纤维细胞的亡反应减少,并阻止体内Caspase 3的激活.
结论:
- 在胚胎大脑中,Apaf1对于卡斯帕酶3的激活至关重要.
- 在哺乳动物中,Apaf1在调节发育编程细胞死亡方面发挥着关键作用.
- 缺少Apaf1会导致严重的发育缺陷和胚胎死亡.
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...
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...
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...


