H2O2-treated actin: Assembly and polymer interactions with cross-linking proteins
H2O2-treated actin: Assembly and polymer interactions with cross-linking proteins
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DOI：
10.1016/s0006-3495(95)80142-6
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发表时间：
1995-12-01
影响因子：
3.4
通讯作者：
Colombo, R
中科院分区：
文献类型：
--
作者：
DalleDonne, I;Milzani, A;Colombo, R
在炎症过程中，多形核白细胞产生的过氧化氢主要通过扰乱丝状（聚合）肌动蛋白（F-肌动蛋白）引起细胞死亡。为了显示过氧化氢改变肌动蛋白动力学的分子机制，我们分析了H2 O2处理的肌动蛋白样品的交联能力以及肌动蛋白聚合物（来自氧化单体）与交联蛋白相互作用的适用性。H2 O2处理的单体（球状）肌动蛋白（G-肌动蛋白）显示出改变的时间过程的聚合。滞后期的增加和聚合速率和聚合程度的降低已被证明，此外，稳态肌动蛋白聚合物，从氧化单体，比对照聚合物更碎片化。这似乎是由于氧化丝的脆性增强，而不是成核活性的增加，显着福尔斯下降。这些事实，沿着不适合的肌动蛋白聚合物从氧化单体相互作用的细丝蛋白和r-辅肌动蛋白，表明过氧化氢影响肌动蛋白动力学主要是通过改变F-肌动蛋白的结构。过氧化氢，通过氧化的肌动蛋白硫醇（特别是巯基Cys-374），可能会改变肌动蛋白的C-末端，影响两个亚基/亚基的相互作用和空间结构的结合位点的交联蛋白在F-肌动蛋白。我们认为，大多数过氧化氢对肌动蛋白的影响可以解释在光的“结构连接”，以前在肌动蛋白中证明。
During inflammation, hydrogen peroxide, produced by polymorphonuclear leukocytes, provokes cell death mainly by disarranging filamentous (polymerized) actin (F-actin). To show the molecular mechanism(s) by which hydrogen peroxide could alter actin dynamics, we analyzed the ability of H2O2-treated actin samples to polymerize as well as the suitability of actin polymers (from oxidized monomers) to interact with cross-linking proteins. H2O2-treated monomeric (globular) actin (G-actin) shows an altered time course of polymerization. The increase in the lag phase and the lowering in both the polymerization rate and the polymerization extent have been evidenced, furthermore, steady-state actin polymers, from oxidized monomers, are more fragmented than control polymers. This seems to be ascribable to the enhanced fragility of oxidized filaments rather than to the increase in the nucleation activity, which markedly falls. These facts, along with the unsuitability of actin polymers from oxidized monomers to interact with both filamin and rr-actinin, suggest that hydrogen peroxide influences actin dynamics mainly by changing the F-actin structure. H2O2, via the oxidation of actin thiols (in particular, the sulfhydryl group of Cys-374), likely alters the actin C-terminus, influencing both subunit/subunit interactions and the spatial structure of the binding sites for cross-linking proteins in F-actin. We suggest that most of the effects of hydrogen peroxide on actin could be explained in the light of the ''structural connectivity,'' demonstrated previously in actin.