Oxidative stress pathogenically remodels the cardiac myocyte cytoskeleton via structural alterations to the microtubule lattice.
Oxidative stress pathogenically remodels the cardiac myocyte cytoskeleton via structural alterations to the microtubule lattice.
复制标题
氧化应激通过微管晶格的结构改变致病性地重塑心肌细胞的细胞骨架。
DOI：
10.1016/j.devcel.2021.07.004
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发表时间：
2021-08-09
影响因子：
11.8
通讯作者：
Gardner MK
中科院分区：
文献类型：
--
作者：
Goldblum RR;McClellan M;White K;Gonzalez SJ;Thompson BR;Vang HX;Cohen H;Higgins L;Markowski TW;Yang TY;Metzger JM;Gardner MK
在衰竭的心脏中，心肌细胞微管网络被重构，这导致细胞收缩衰竭和患者死亡。然而，这种有害的细胞骨架重组的起源是未知的。我们现在发现，氧化应激，一种心力衰竭的特征，导致微管的半胱氨酸氧化。我们的电子显微镜和荧光显微镜实验显示，在氧化微管蛋白的位置发生的微管晶格内的结构损伤的区域。将GTP-微管蛋白掺入这些受损的氧化区域导致微管晶格内稳定的“热点”，这抑制了动态微管的缩短。因此，氧化应激可能在心肌细胞内起作用，以促进从稀疏的微管网络到密集的排列网络的致病性转变。我们的研究结果表明，以氧化应激为特征的疾病如何引发分子氧化事件，这可能有助于心肌细胞微管网络的毒性细胞规模转化。Goldblum等人证明氧化应激导致微管蛋白的半胱氨酸氧化，这与微管晶格的损伤有关。在存在游离微管蛋白的情况下，这种损伤用GTP-微管蛋白修复，从而抑制微管解聚。因此，氧化应激可促进心肌细胞中微管网络的致密化。
In the failing heart, the cardiac myocyte microtubule network is remodeled, which contributes to cellular contractile failure and patient death. However, the origins of this deleterious cytoskeletal reorganization are unknown. We now find that oxidative stress, a condition characteristic of heart failure, leads to cysteine oxidation of microtubules. Our electron and fluorescence microscopy experiments revealed regions of structural damage within the microtubule lattice that occurred at locations of oxidized tubulin. The incorporation of GTP-tubulin into these damaged, oxidized regions led to stabilized “hot spots” within the microtubule lattice, which suppressed the shortening of dynamic microtubules. Thus, oxidative stress may act inside of cardiac myocytes to facilitate a pathogenic shift from a sparse microtubule network into a dense, aligned network. Our results demonstrate how a disease condition characterized by oxidative stress can trigger a molecular oxidation event, which likely contributes to a toxic cellular-scale transformation of the cardiac myocyte microtubule network. Goldblum et al. demonstrate that oxidative stress leads to cysteine oxidation of tubulin, which is associated with damage to the microtubule lattice. In the presence of free tubulin, this damage is repaired with GTP-Tubulin, thus suppressing microtubule depolymerization. Thus, oxidative stress may facilitate densification of the microtubule network in cardiomyocytes.
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影响因子：
2.7
作者：
Hu, Wei-Guo;Lu, Qi-Ping
通讯作者：
Lu, Qi-Ping
影响因子：
2.9
作者：
HINSHAW, DB;MILLER, MT;HYSLOP, PA
通讯作者：
HYSLOP, PA
影响因子：
5.5
作者：
Fearon, IM;Palmer, ACV;Peers, C
通讯作者：
Peers, C
DOI：
10.1073/pnas.81.3.771
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CARLIER, MF;HILL, TL;CHEN, YD
通讯作者：
CHEN, YD
影响因子：
64.5
作者：
Gardner MK;Charlebois BD;Jánosi IM;Howard J;Hunt AJ;Odde DJ
通讯作者：
Odde DJ