Diverse protective roles of the actin cytoskeleton during oxidative stress.
Diverse protective roles of the actin cytoskeleton during oxidative stress.
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DOI：
10.1002/cm.20516
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发表时间：
2011-06
期刊：
影响因子：
2.9
通讯作者：
Amberg, David C.
中科院分区：
文献类型：
--
作者：
Farah, Michelle E.;Sirotkin, Vladimir;Haarer, Brian;Kakhniashvili, David;Amberg, David C.
已知肌动蛋白氧化会导致细胞骨架组织和动力学的变化。肌动蛋白氧化与临床相关，因为它发生在镰状细胞患者的红细胞中，并且可能是在不可逆镰状红细胞（ISCs）中观察到的缺乏形态可塑性的直接原因。在危机发作期间，ISCs积累C284-C373分子内二硫键合肌动蛋白，这降低了肌动蛋白丝的动力学。肌动蛋白半胱氨酸284和373（酵母中的285和374）是保守的，表明它们起着重要的功能作用。我们一直在用真核生物酿酒酵母模型研究这些半胱氨酸在氧化应激负荷下的生理作用。在急性氧化应激期间，野生型细胞中所有的f -肌动蛋白都会坍塌成几个点，我们称之为氧化肌动蛋白体（OABs）。相比之下，在急性氧化应激中，Cys-to-Ala肌动蛋白突变体的肌动蛋白细胞骨架保持极化的时间更长，oab的形成速度更慢，细胞的恢复速度也比野生型细胞慢，这表明oab具有保护作用。活细胞成像显示，oab是一种含有肌动蛋白结合蛋白的大型固定结构，可以通过肌动蛋白皮质斑块的融合形成。我们提出肌动蛋白C285和C374可能有助于保护细胞免受正常氧化代谢引起的氧化应激，并有助于细胞对氧化应激的一般适应性反应。
Actin oxidation is known to result in changes in cytoskeleton organization and dynamics. Actin oxidation is clinically relevant since it occurs in the erythrocytes of sickle cell patients and may be the direct cause of the lack of morphological plasticity observed in irreversibly sickled red blood cells (ISCs). During episodes of crisis, ISCs accumulate C284-C373 intra-molecularly disulfide bonded actin, which reduces actin filament dynamics. Actin cysteines 284 and 373 (285 and 374 in yeast) are conserved, suggesting that they play an important functional role. We have been investigating the physiological roles of these cysteines using the model eukaryote S. cerevisiae in response to oxidative stress load. During acute oxidative stress, all of the F-actin in wild type cells collapses into a few puncta that we call oxidized actin bodies (OABs). In contrast, during acute oxidative stress the actin cytoskeleton in Cys-to-Ala actin mutants remains polarized longer, OABs are slower to form, and the cells recover more slowly than wild type cells, suggesting that the OABs play a protective role. Live cell imaging revealed that OABs are large, immobile structures that contain actin binding proteins and that can form by the fusion of actin cortical patches. We propose that actin’s C285 and C374 may help to protect the cell from oxidative stress arising from normal oxidative metabolism and contribute to the cell’s general adaptive response to oxidative stress.
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