School of Pharmacy, Faculty of Medicine, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
Sci Rep. 2020 Aug 17;10(1):13913. doi: 10.1038/s41598-020-70383-6.
Cell aging depends on the rate of cumulative oxidative and nitrosative damage to DNA and proteins. Accumulated data indicate the involvement of protein S-nitrosylation (SNO), the nitric oxide (NO)-mediated posttranslational modification (PTM) of cysteine thiols, in different brain disorders. However, the changes and involvement of SNO in aging including the development of the organism from juvenile to adult state is still unknown. In this study, using the state-of-the-art mass spectrometry technology to identify S-nitrosylated proteins combined with large-scale computational biology, we tested the S-nitroso-proteome in juvenile and adult mice in both cortical and striatal regions. We found reprogramming of the S-nitroso-proteome in adult mice of both cortex and striatum regions. Significant biological processes and protein-protein clusters associated with synaptic and neuronal terms were enriched in adult mice. Extensive quantitative analysis revealed a large set of potentially pathological proteins that were significantly upregulated in adult mice. Our approach, combined with large scale computational biology allowed us to perform a system-level characterization and identification of the key proteins and biological processes that can serve as drug targets for aging and brain disorders in future studies.
细胞衰老取决于 DNA 和蛋白质累积的氧化和硝化损伤的速度。累积的数据表明，蛋白质 S-亚硝基化（SNO），即一氧化氮（NO）介导的半胱氨酸巯基的翻译后修饰（PTM），参与了不同的脑疾病。然而，SNO 在衰老中的变化和作用，包括生物体从幼年到成年状态的发育，仍然未知。在这项研究中，我们使用最先进的质谱技术来鉴定 S-亚硝基化蛋白质，并结合大规模计算生物学，在皮质和纹状体区域的幼年和成年小鼠中测试 S-亚硝酰基蛋白质组。我们发现，成年小鼠的 S-亚硝酰基蛋白质组发生了重新编程。与突触和神经元术语相关的显著生物学过程和蛋白质-蛋白质簇在成年小鼠中得到了富集。广泛的定量分析揭示了一组大量潜在的病理蛋白，这些蛋白在成年小鼠中显著上调。我们的方法结合大规模计算生物学，使我们能够对关键蛋白质和生物学过程进行系统水平的表征和鉴定，这些蛋白质和生物学过程可以作为未来研究中衰老和脑疾病的药物靶点。
