Zakusov Research Institute of Pharmacology, Moscow, Russia.
Institute of Biochemistry and Genetics, Subdivision of the Ufa Federal Research Center, Russian Academy of Sciences, Ufa, Russia.
Dokl Biochem Biophys. 2020 Sep;494(1):256-260. doi: 10.1134/S1607672920050129. Epub 2020 Oct 20.
The effect of noopept (N-phenylacetyl-L-prolyl-glycine ethyl ester) on the DNA-binding activity of HIF-1 in SH-SH5Y cells and the mechanisms of stabilization of this transcription factor were studied in vitro. Noopept was shown to increase both the basal DNA-binding activity of HIF-1 and the activity induced by various hypoxia mimetics. The mechanism of stabilization of the oxygen-sensitive HIF1α subunit by noopept involves the inhibition of HIF-1 prolyl hydroxylase, which is indirectly indicated by the data obtained using the ODD-Luc reporter, and the positive effect on the level of the HIF1α protein. It was revealed that the effect of noopept is accompanied by changes in gene expression, which belong to different metabolic pathways and are controlled by the transcription factor HIF-1.
研究了新型益智药(N-苯乙酰-L-脯氨酰-甘氨酸乙酯)对 SH-SH5Y 细胞中 HIF-1 的 DNA 结合活性的影响及其稳定这种转录因子的机制。结果表明,该药物既能增加 HIF-1 的基础 DNA 结合活性,又能增加各种低氧模拟物诱导的活性。益智药稳定氧敏感型 HIF1α 亚基的机制涉及抑制 HIF-1 脯氨酰羟化酶,这从使用 ODD-Luc 报告基因获得的数据间接表明,并且对 HIF1α 蛋白水平有积极影响。结果表明,益智药的作用伴随着基因表达的变化,这些变化属于不同的代谢途径,并受转录因子 HIF-1 的控制。