Experimental traumatic brain injury increases epichaperome formation.
Experimental traumatic brain injury increases epichaperome formation.
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DOI：
10.1016/j.nbd.2023.106331
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发表时间：
2023-11
影响因子：
6.1
通讯作者：
Dixon, C. Edward
中科院分区：
文献类型：
--
作者：
Svirsky, Sarah E.;Li, Youming;Henchir, Jeremy;Rodina, Anna;Carlson, Shaun W.;Chiosis, Gabriela;Dixon, C. Edward
在正常条件下，热休克蛋白通过统称为“伴侣组”的动态蛋白质相互作用协同工作。最近的研究表明，在细胞应激过程中，伴侣蛋白的功能相互作用被修改，形成“外伴侣蛋白”，从而导致蛋白质折叠、降解、聚集和运输不当。这项研究首次研究了创伤性脑损伤（TBI）中蛋白质失衡的这种新机制。雄性和雌性成年 Sprague-Dawley 大鼠接受侧向控制皮质冲击 (CCI)，并在损伤后 24 小时、1、2 和 4 周收集同侧海马。通过测量非变性 PAGE 中的 HSP90、HSC70 和 HOP 表达来可视化外表面复合体，并将其标准化为单体蛋白表达。双向方差分析检查了每个时间点的伤害和性的影响。天然 HSP90、HSC70 和 HOP 蛋白表达在所有时间点均显示出损伤效应的显着影响。此外，HSC70 和 HOP 在 24 小时和 4 周时显示出显着的性别影响。总而言之，受控的皮质影响显着增加了所有测量蛋白质的外表面组的形成。对这种病理机制的进一步研究可以更好地了解 TBI 与神经退行性疾病风险增加之间的联系，并针对表层体进行治疗。
Under normal conditions, heat shock proteins work in unison through dynamic protein interactions collectively referred to as the “chaperome.” Recent work revealed that during cellular stress, the functional interactions of the chaperome are modified to form the “epichaperome,” which results in improper protein folding, degradation, aggregation, and transport. This study is the first to investigate this novel mechanism of protein dishomeostasis in traumatic brain injury (TBI). Male and female adult, Sprague-Dawley rats received a lateral controlled cortical impact (CCI) and the ipsilateral hippocampus was collected 24 h 1, 2, and 4 weeks after injury. The epichaperome complex was visualized by measuring HSP90, HSC70 and HOP expression in native-PAGE and normalized to monomeric protein expression. A two-way ANOVA examined the effect of injury and sex at each time-point. Native HSP90, HSC70 and HOP protein expression showed a significant effect of injury effect across all time-points. Additionally, HSC70 and HOP showed significant sex effects at 24 h and 4 weeks. Altogether, controlled cortical impact significantly increased formation of the epichaperome across all proteins measured. Further investigation of this pathological mechanism can lead to a greater understanding of the link between TBI and increased risk of neurodegenerative disease and targeting the epichaperome for therapeutics.
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影响因子：
4.7
作者：
Eroglu B;Kimbler DE;Pang J;Choi J;Moskophidis D;Yanasak N;Dhandapani KM;Mivechi NF
通讯作者：
Mivechi NF
影响因子：
4.2
作者：
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通讯作者：
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影响因子：
4.2
作者：
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Pavel, KM
影响因子：
82.9
作者：
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通讯作者：
Cuervo, Ana Maria
影响因子：
16.6
作者：
Bolaender A;Zatorska D;He H;Joshi S;Sharma S;Digwal CS;Patel HJ;Sun W;Imber BS;Ochiana SO;Patel MR;Shrestha L;Shah SK;Wang S;Karimov R;Tao H;Patel PD;Martin AR;Yan P;Panchal P;Almodovar J;Corben A;Rimner A;Ginsberg SD;Lyashchenko S;Burnazi E;Ku A;Kalidindi T;Lee SG;Grkovski M;Beattie BJ;Zanzonico P;Lewis JS;Larson S;Rodina A;Pillarsetty N;Tabar V;Dunphy MP;Taldone T;Shimizu F;Chiosis G
通讯作者：
Chiosis G