Abstract

Postgenomic pharmacology deals with the desirable and undesirable effects of drugs in relation to the genome, transcriptome, proteome, and reactome. The transcriptomic activity of ethylmethylhydroxypyridine succinate (EMHPS) has not been previously characterized.Objective: to investigate the dose-dependent effects of EMHPS on the transcription of 12,700 annotated human genes in the neural progenitor cells (NPC.TAK cell line).Material and methods. The paper presents the results of chemotranscriptome analysis of the EMHPS molecule from the point of view of its impact on transcription of the human genome in the NPC.TAK line cells during 24-hour incubation of cells with EMHPS.Results and discussion. The significant dose-dependent effects of EMHPS on transcription (on average, ≥10% transcription changes for each 1 μmol/L of EMHPS) were evaluated for 2,400 of the 12,700 annotated human genes. EMHPS reduced the transcription of groups of the genes that were involved in cell division (n = 226), those in gene expression processes (n = 122), and those in protein synthesis, degradation, and secretion (n = 123). EMHPS increased the transcription of the genes encoding proteins involved in neurotransmission (n = 103) and those in exerting neuroprotective and neurotrophic effects (n = 49).Conclusion. The efficacy of EMHPS may be related to its effect on the transcription of the genes that are involved in neurotransmission and in the showing of neuroprotective and neurotrophic effects.

Highlights

  • Chemotranscriptome analysis of the ethylmethylhydroxypyridine succinate molecule in the context of postgenomic pharmacology Gromova O.A.1, 2, Torshin I.Yu.1, 2, Sorokin A.I.2, Semenov V.A.3, Stakhovskaya L.V.4

  • The paper presents the results of chemotranscriptome analysis of the ethylmethylhydroxypyridine succinate (EMHPS) molecule from the point of view of its impact on transcription of the human genome in the NPC.TAK line cells during 24-hour incubation of cells with EMHPS

  • EMHPS reduced the transcription of groups of the genes that were involved in cell division (n = 226), those in gene expression processes (n = 122), and those in protein synthesis, degradation, and secretion (n = 123)

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Summary

ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ

Громова О.А.1, 2, Торшин И.Ю.1, 2, Сорокин А.И.2, Семенов В.А.3, Стаховская Л.В.4 1Институт фармакоинформатики Федерального исследовательского центра «Информатика и управление» Российской академии наук, Москва; 2Центр хранения и анализа больших данных Национального центра цифровой экономики ФГБОУ ВО «Московский государственный университет им. Цель исследования – изучение дозозависимых эффектов воздействия ЭМПГС на транскрипцию 12 700 аннотированных генов человека в клетках-предшественниках нейронов (клеточная линия NPC.TAK). Представлены результаты хемотранскриптомного анализа молекулы ЭМПГС с точки зрения влияния на транскрипцию генома человека в клетках линии NPC.TAK при инкубации клеток с ЭМГПС в течение 24 ч. Достоверные дозозависимые эффекты влияния ЭМГПС на транскрипцию (в среднем ≥10% изменения транскрипции на каждый 1 мкмоль/л ЭМПГС) были оценены для 2400 из 12 700 аннотированных генов человека. Objective: to investigate the dose-dependent effects of EMHPS on the transcription of 12,700 annotated human genes in the neural progenitor cells (NPC.TAK cell line). The paper presents the results of chemotranscriptome analysis of the EMHPS molecule from the point of view of its impact on transcription of the human genome in the NPC.TAK line cells during 24-hour incubation of cells with EMHPS.

Conclusion
TORC киназы
Экспрессия достоверно повышена
Необходим для биогенеза миелина
Full Text
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