PDF(Pubmed)
Abstract：
Oral poisoning can trigger diverse physiological reactions, determined by the toxic substance involved. One such consequence is hyperchloremia, characterized by an elevated level of chloride in the blood and leads to kidney damage and impairing chloride ion regulation. Here, we conducted a comprehensive genome-wide analysis to investigate genes or proteins linked to hyperchloremia. Our analysis included functional enrichment, protein-protein interactions, gene expression, exploration of molecular pathways, and the identification of potential shared genetic factors contributing to the development of hyperchloremia. Functional enrichment analysis revealed that oral poisoning owing hyperchloremia is associated with 4 proteins e.g. Kelch-like protein 3, Serine/threonine-protein kinase WNK4, Serine/threonine-protein kinase WNK1 and Cullin-3. The protein-protein interaction network revealed Cullin-3 as an exceptional protein, displaying a maximum connection of 18 nodes. Insufficient data from transcriptomic analysis indicates that there are lack of information having direct associations between these proteins and human-related functions to oral poisoning, hyperchloremia, or metabolic acidosis. The metabolic pathway of Cullin-3 protein revealed that the derivative is Sulfonamide which play role in, increasing urine output, and metabolic acidosis resulted in hypertension. Based on molecular docking results analysis it found that Cullin-3 proteins has the lowest binding energies score and being suitable proteins. Moreover, no major variations were observed in unbound Cullin-3 and all three peptide bound complexes shows that all systems remain compact during 50 ns simulations. The results of our study revealed Cullin-3 proteins be a strong foundation for the development of potential drug targets or biomarker for future studies.
摘要：
口腔中毒可引发多种生理反应,由所涉及的有毒物质决定。这样的后果之一是高氯血症，其特征是血液中氯化物水平升高，导致肾脏损害和氯离子调节受损。这里,我们进行了一项全面的全基因组分析,以调查与高氯血症相关的基因或蛋白质.我们的分析包括功能富集，蛋白质-蛋白质相互作用，基因表达，探索分子途径，以及鉴定导致高氯血症发展的潜在共有遗传因素。功能富集分析显示，高氯血症引起的口服中毒与4种蛋白质有关，例如Kelch样蛋白3，丝氨酸/苏氨酸蛋白激酶WNK4，丝氨酸/苏氨酸蛋白激酶WNK1和Cullin-3。蛋白质-蛋白质相互作用网络揭示了Cullin-3是一种特殊的蛋白质，显示18个节点的最大连接。转录组学分析的数据不足表明，缺乏这些蛋白质与人类相关功能与口服中毒之间直接相关的信息，高氯血症,或者代谢性酸中毒.Cullin-3蛋白的代谢途径显示其衍生物为磺胺,增加尿量,代谢性酸中毒导致高血压。基于分子对接结果分析,发现Cullin-3蛋白具有最低的结合能得分并且是合适的蛋白。此外，在未结合的Cullin-3中未观察到主要变化，并且所有三种肽结合的复合物显示所有系统在50ns模拟期间保持紧凑。我们的研究结果表明，Cullin-3蛋白是开发潜在药物靶标或未来研究生物标志物的坚实基础。
