■虽然原癌基因小GTPasesRas是氧化还原敏感蛋白,它们是如何通过中枢神经系统(CNS)的氧化还原信号调节的,仍然知之甚少。氧化还原信号对氧化还原敏感靶标的改变可能对Ras稳定性产生无数影响,活动和本地化。星形细胞RAS的氧化还原介导的变化可能有助于控制CNS中的氧化还原稳态,这与许多疾病的发病机理有关。
■这里,我们研究了短暂的生理诱导,在转录和翻译水平,响应氧化还原刺激的小GTP酶Ras。培养的星形胶质细胞用过氧化氢处理,如推注添加,并通过qRT-PCR检测鼠hras和kras基因的相对mRNA水平。我们发现反应性星形胶质细胞中hrasmRNA的从头转录对氧化还原敏感,并模拟了典型的氧化还原敏感基因iNOS。蛋白质丰度与通过环己酰亚胺追踪实验进行的蛋白质周转测量相结合,揭示了不同的翻译效率,结合GTP的富集,和两种亚型H-Ras和K-Ras之间的蛋白质转换率。
■近年来的报告支持H-Ras在驱动氧化还原过程中的重要作用。除了其规范功能之外,Ras可能会影响在氧化还原刺激期间起作用的核心星形细胞机制。
UNASSIGNED: Although the protooncogenes small GTPases Ras are redox-sensitive proteins, how they are regulated by redox signaling in the central nervous system (CNS) is still poorly understood. Alteration in redox-sensitive targets by redox signaling may have myriad effects on Ras stability, activity and localization. Redox-mediated changes in astrocytic RAS may contribute to the control of redox homeostasis in the CNS that is connected to the pathogenesis of many diseases.
UNASSIGNED: Here, we investigated the transient physiological induction, at both transcriptional and translational levels, of small GTPases Ras in response to redox stimulation. Cultured astrocytes were treated with hydrogen peroxide as in bolus addition and relative mRNA levels of murine hras and kras genes were detected by qRT-PCR. We found that de novo transcription of hras mRNA in reactive astrocytes is redox-sensitive and mimics the prototypical redox-sensitive gene iNOS. Protein abundance in combination with protein turnover measurements by cycloheximide-chase experiments revealed distinct translation efficiency, GTP-bound enrichment, and protein turnover rates between the two isoforms H-Ras and K-Ras.
UNASSIGNED: Reports from recent years support a significant role of H-Ras in driving redox processes. Beyond its canonical functions, Ras may impact on the core astrocytic cellular machinery that operates during redox stimulation.