在活细胞中通过HOCl激化甘-3-酸脱酶的激化
Sandra E Gomez-Mejiba1, Zili Zhai1,2, Marcos D Muñoz1,3
1Laboratory of Experimental Therapeutics-IMIBIO-SL-CONICET and School of Health Sciences, National University of San Luis, San Luis, San Luis 5700, Argentina.
概括
一种新型的自由基机制,涉及到由髓氧化酶衍生的低酸,在脂多糖素原料细胞中使甘甲基-3-酸脱酶 (GAPDH) 失活,从而导致细胞死亡.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 自由基化学 自由基化学
背景情况:
- 甘-3-酸盐脱酶 (GAPDH) 是一个关键的糖解酶和氧化还原传感器.
- GAPDH的翻译后氧化修饰会影响细胞命运,但自由基机制以前没有报道.
- RAW264.7细胞的脂聚糖化物 (LPS) 起始激活炎症反应.
研究的目的:
- 调查一种新的自由基机制,它是GAPDH无活化和聚合的基础.
- 阐明髓氧化酶 (MPO) 和低酸 (HOCl) 在这个过程中的作用.
- 为了确定GAPDH上激进化的特定地点.
主要方法:
- 采用了基于子5,5-二甲基-1-氨酸N-氧化物 (DMPO) 的旋转捕获技术.
- 在LPS原料RAW264.7细胞中检查了GAPDH修饰.
- 分析了酶活性,聚合,乳酸积累和细胞死亡.
主要成果:
- 发现了一种新的自由基机制,导致GAPDH无活化和聚合.
- 氧化酶 (MPO) 衍生的低酸 (HOCl) 在LPS原始细胞中氧化GAPDH.
- GAPDH的激进化,特别是氨酸残留物,与酶失活,乳酸积累和细胞死亡相关.
结论:
- 低酸 (HOCl) 是一个关键的媒介,触发GAPDH激进化和随后的酶失活和聚合在LPS原料巨细胞中.
- GAPDH的激进化与炎症期间应激细胞的命运有关.
- 了解这种机制,可以了解在炎症环境中细胞对压力的反应.
相关概念视频
Radical Reactivity: Electrophilic Radicals
1.8K
Radicals adjacent to electron‐withdrawing groups are called electrophilic radicals. These radicals readily react with nucleophilic alkenes. For example, the malonate radical, in which the radical center is flanked by two electron‐withdrawing groups, reacts readily with butyl vinyl ether, which consists of an electron‐donating oxygen substituent. The reaction between electrophilic malonate radical and nucleophilic vinyl ether is favored because the radical has a...
1.8K
Radical Formation: Homolysis
3.5K
A bond is formed between two atoms by sharing two electrons. When this bond is broken by supplying sufficient energy, either two electrons can be taken up by one atom forming ions by the cleavage called heterolysis, or the two electrons are shared by two atoms, with one each creating radicals by the cleavage called homolysis.
3.5K
Radical Formation: Elimination
1.7K
Another method of radical formation is the elimination process. It is the opposite of the addition route and is driven by the instability of the radical. For example, as depicted in Figure 1, dibenzoyl peroxide yields a pair of unstable radicals upon homolysis. Given its instability, this radical spontaneously undergoes elimination via a C–C bond cleavage to form a relatively more stable phenyl radical. The mechanism involves cleavage of the bond between the α and β positions...
1.7K
Radical Formation: Abstraction
3.5K
The electron of an atom can be abstracted from a compound by a relatively unstable radical to generate a new radical of relatively greater stability. For example, an initiator which forms radicals by homolysis can abstract a suitable species like a hydrogen atom or a halogen atom from a compound to generate a new radical. This ability of radicals to propagate by abstraction is a crucial feature of radical chain reactions.
Even though homolysis produces radicals, it is different from radical...
Even though homolysis produces radicals, it is different from radical...
3.5K
Radical Autoxidation
2.1K
The oxidation of an organic compound in the presence of air or oxygen is called autoxidation. For example, cumene reacts with oxygen to form hydroperoxide. Autoxidation involves initiation, propagation, and termination steps. Many organic compounds are susceptible to autoxidation—especially ethers in the presence of oxygen, which form hydroperoxides. Even though this reaction is slow, old ether bottles contain small amounts of peroxide, which leads to laboratory explosions during ether...
2.1K
Radical Substitution: Allylic Chlorination
2.2K
Typically, when alkenes react with halogens at low temperatures, an addition reaction occurs. However, upon increasing the temperature or under reaction conditions that form radicals, providing a low but steady concentration of halogen radicals, allylic substitution reaction is favored. This is because allylic hydrogens are very reactive as the formed intermediate is resonance stabilized. For example, when propene is treated with chlorine in the gas phase at 400 °C, it undergoes allylic...
2.2K


