Bjørkum Alvhild Alette, Oveland Eystein, Stuhr Linda, Havnes Marianne Bjordal, Berven Frode, Grønning Marit, Hope Arvid
Department of Biomedical Laboratory Sciences and Chemical Engineering, Western Norway University of Applied Sciences, Bergen, Norway.
Proteomics Unit at the University of Bergen, Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
PLoS One. 2017 Oct 4;12(10):e0185765. doi: 10.1371/journal.pone.0185765. eCollection 2017.
Better understanding of the physiological mechanisms and neurological symptoms involved in the development of decompression sickness could contribute to improvements of diving procedures. The main objective of the present study was to determine effects on the brain proteome of fast decompression (1 bar/20 s) compared to controls (1 bar/10 min) after heliox saturation diving, using rats in a model system. The protein S100B, considered a biomarker for brain injury, was not significantly different in serum samples from one week before, immediately after, and one week after the dive. Alterations in the rat brain proteome due to fast decompression were investigated using both iontrap and orbitrap LC-MS, and 967 and 1062 proteins were quantified, respectively. Based on the significantly regulated proteins in the iontrap (56) and orbitrap (128) datasets, the networks "synaptic vesicle fusion and recycling in nerve terminals" and "translation initiation" were significantly enriched in a system biological database analysis (Metacore). Ribosomal proteins (RLA2, RS10) and the proteins hippocalcin-like protein 4 and proteasome subunit beta type-7 were significantly upregulated in both datasets. The heat shock protein 105 kDa, Rho-associated protein kinase 2 and Dynamin-1 were significantly downregulated in both datasets. Another main effect of hyperbaric fast decompression in our experiment is inhibition of endocytosis and stimulation of exocytosis of vesicles in the presynaptic nerve terminal. In addition, fast decompression affected several proteins taking parts in these two main mechanisms of synaptic strength, especially alteration in CDK5/calcineurin are associated with a broad range of neurological disorders. In summary, fast decompression after heliox saturation affected the brain proteome in a rat model for diving, potentially disturbing protein homeostasis, e.g. in synaptic vesicles, and destabilizing cytoskeletal components. Data are available via ProteomeXchange with identifier PXD006349.
更好地理解减压病发展过程中涉及的生理机制和神经症状,可能有助于改进潜水程序。本研究的主要目的是,在氦氧饱和潜水后,使用大鼠模型系统,确定快速减压(1巴/20秒)相比于对照组(1巴/10分钟)对大脑蛋白质组的影响。被认为是脑损伤生物标志物的蛋白质S100B,在潜水前一周、潜水后即刻以及潜水后一周的血清样本中并无显著差异。利用离子阱和轨道阱液相色谱-质谱联用技术研究了快速减压引起的大鼠大脑蛋白质组变化,分别定量了967种和1062种蛋白质。基于离子阱(56种)和轨道阱(128种)数据集中显著调控的蛋白质,在系统生物学数据库分析(Metacore)中,“神经末梢中的突触小泡融合与循环利用”和“翻译起始”网络显著富集。核糖体蛋白(RLA2、RS10)以及类海马钙蛋白4和蛋白酶体β7亚基在两个数据集中均显著上调。105 kDa热休克蛋白、Rho相关蛋白激酶2和发动蛋白1在两个数据集中均显著下调。我们实验中高压快速减压的另一个主要影响是抑制突触前神经末梢的内吞作用并刺激小泡的外排作用。此外,快速减压影响了参与突触强度这两种主要机制的几种蛋白质,尤其是CDK5/钙调神经磷酸酶的改变与多种神经疾病有关。总之,氦氧饱和后的快速减压在潜水大鼠模型中影响了大脑蛋白质组,可能扰乱蛋白质稳态,如突触小泡中的蛋白质稳态,并破坏细胞骨架成分的稳定性。数据可通过ProteomeXchange获得,标识符为PXD006349。