Changes of Transcriptomic Activity in Rat Brain Cells under the Influence of Synthetic Adrenocorticotropic Hormone-Like Peptides

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ivan B. Filippenkov, Nataliya Y. Glazova, Elena A. Sebentsova, Vasily V. Stavchansky, Lyudmila A. Andreeva, Nikolai F. Myasoedov, Nataliya G. Levitskaya, Svetlana A. Limborska, Lyudmila V. Dergunova
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Abstract

Synthetic peptides have a wide range of clinical effects. Of particular interest are peptides based on adrenocorticotropic hormone (ACTH) both as already used and as potential drugs for preventing consequences of cerebral ischemia. However, it is necessary to study influence of the peptide on the brain cells under normal physiological conditions, including understanding the risks of their use. Here, we used high-throughput RNA sequencing (RNA-Seq) to identify differentially expressed genes (DEGs) in the brain frontal cortex of rat receiving intraperitoneal administration of ACTH-like peptides ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP, or saline. We identified 258 and 228 DEGs, respectively, with the fold change > 1.5 and Padj < 0.05 at 22.5 h after the first administration of Semax and ACTH(6-9)PGP. Metabolic pathways, characterizing both common and specific effects of the peptides on the transcriptome were identified. Both peptides predominantly caused decrease in expression of the genes associated with the immune system. At the same time, when comparing the effects of ACTH(6-9)PGP relative to Semax, DEGs were identified that characterized the main differences in the effects of the peptides. These genes were mostly downregulated and associated with neurosignaling systems and regulation of ion channels, thus characterizing differences in the effects of the peptides. Our data show how differences in the structure of ACTH derivatives are associated with the changes in the brain cell transcriptome following exposure to these related peptides. Furthermore, our results demonstrate that when studying influence of regulatory peptides on transcriptome under pathological conditions, it is necessary to take into account their actions under normal physiological conditions.

合成促肾上腺皮质激素样肽影响下大鼠脑细胞转录组活性的变化
合成肽具有广泛的临床效果。特别令人感兴趣的是基于促肾上腺皮质激素(ACTH)的合成肽,这种合成肽既可作为已使用的药物,也可作为预防脑缺血后果的潜在药物。然而,有必要研究肽在正常生理条件下对脑细胞的影响,包括了解其使用风险。在此,我们利用高通量 RNA 测序(RNA-Seq)技术,鉴定了腹腔注射促肾上腺皮质激素样肽 ACTH(4-7)PGP (Semax) 和 ACTH(6-9)PGP 或生理盐水的大鼠大脑额叶皮层中的差异表达基因(DEGs)。我们分别鉴定出了 258 个和 228 个 DEGs,它们在首次给予 Semax 和 ACTH(6-9)PGP 后 22.5 h 的折叠变化分别为 1.5 倍和 0.05 倍。研究人员确定了代谢通路,这些通路体现了肽对转录组的共同作用和特殊作用。这两种肽主要导致与免疫系统相关的基因表达量减少。与此同时,在比较 ACTH(6-9)PGP 与 Semax 的影响时,还发现了这两种肽的主要影响差异的 DEGs。这些基因大多被下调,并与神经信号系统和离子通道调控有关,从而描述了多肽效应的差异。我们的数据显示了促肾上腺皮质激素衍生物结构的差异如何与暴露于这些相关肽后脑细胞转录组的变化相关联。此外,我们的研究结果表明,在研究病理条件下调节肽对转录组的影响时,有必要考虑它们在正常生理条件下的作用。
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来源期刊
Biochemistry (Moscow)
Biochemistry (Moscow) 生物-生化与分子生物学
CiteScore
4.70
自引率
3.60%
发文量
139
审稿时长
2 months
期刊介绍: Biochemistry (Moscow) is the journal that includes research papers in all fields of biochemistry as well as biochemical aspects of molecular biology, bioorganic chemistry, microbiology, immunology, physiology, and biomedical sciences. Coverage also extends to new experimental methods in biochemistry, theoretical contributions of biochemical importance, reviews of contemporary biochemical topics, and mini-reviews (News in Biochemistry).
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