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Transcriptomic Analysis of the Effect of Torin-2 on the Central Nervous System of Drosophila melanogaster .

التفاصيل البيبلوغرافية
العنوان: Transcriptomic Analysis of the Effect of Torin-2 on the Central Nervous System of Drosophila melanogaster .
المؤلفون: Vershinina YS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Krasnov GS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Garbuz DG; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Shaposhnikov MV; Institute of Biology, Komi Science Center, Ural Branch of RAS, 167000 Syktyvkar, Russia., Fedorova MS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Pudova EA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Katunina IV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Kornev AB; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Zemskaya NV; Institute of Biology, Komi Science Center, Ural Branch of RAS, 167000 Syktyvkar, Russia., Kudryavtsev AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Bulavkina EV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Matveeva AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Ulyasheva NS; Institute of Biology, Komi Science Center, Ural Branch of RAS, 167000 Syktyvkar, Russia., Guvatova ZG; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Anurov AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Moskalev AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia., Kudryavtseva AV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2023 May 22; Vol. 24 (10). Date of Electronic Publication: 2023 May 22.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Drosophila melanogaster*/genetics , Drosophila melanogaster*/metabolism , TOR Serine-Threonine Kinases*/metabolism, Male ; Animals ; Female ; Transcriptome ; Mechanistic Target of Rapamycin Complex 2/metabolism ; Sirolimus/pharmacology ; Central Nervous System/metabolism
مستخلص: Torin-2, a synthetic compound, is a highly selective inhibitor of both TORC1 and TORC2 (target of rapamycin) complexes as an alternative to the well-known immunosuppressor, geroprotector, and potential anti-cancer natural compound rapamycin. Torin-2 is effective at hundreds of times lower concentrations and prevents some negative side effects of rapamycin. Moreover, it inhibits the rapamycin-resistant TORC2 complex. In this work, we evaluated transcriptomic changes in D. melanogaster heads induced with lifetime diets containing Torin-2 and suggested possible neuroprotective mechanisms of Torin-2. The analysis included D. melanogaster of three ages (2, 4, and 6 weeks old), separately for males and females. Torin-2, taken at the lowest concentration being tested (0.5 μM per 1 L of nutrient paste), had a slight positive effect on the lifespan of D. melanogaster males (+4% on the average) and no positive effect on females. At the same time, RNA-Seq analysis revealed interesting and previously undiscussed effects of Torin-2, which differed between sexes as well as in flies of different ages. Among the cellular pathways mostly altered by Torin-2 at the gene expression level, we identified immune response, protein folding (heat shock proteins), histone modification, actin cytoskeleton organization, phototransduction and sexual behavior. Additionally, we revealed that Torin-2 predominantly reduced the expression of Srr gene responsible for the conversion of L-serine to D-serine and thus regulating activity of NMDA receptor. Via western blot analysis, we showed than in old males Torin-2 tends to increase the ratio of the active phosphorylated form of ERK, the lowest node of the MAPK cascade, which may play a significant role in neuroprotection. Thus, the complex effect of Torin-2 may be due to the interplay of the immune system, hormonal background, and metabolism. Our work is of interest for further research in the field of NMDA-mediated neurodegeneration.
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معلومات مُعتمدة: 17-74-30030 (Data analysis) Russian Science Foundation; 19-14-00167 (Western blot analyses) Russian Science Foundation; 075-15-2019-1660 the Ministry of Science and Higher Education of the Russian Federation (Longevity experiments; transcriptome sequencing)
فهرسة مساهمة: Keywords: RNA-Seq; TOR; Torin-2; neurodegeneration; neuroprotection
المشرفين على المادة: EC 2.7.11.1 (TOR Serine-Threonine Kinases)
0 (torin)
EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
W36ZG6FT64 (Sirolimus)
تواريخ الأحداث: Date Created: 20230527 Date Completed: 20230529 Latest Revision: 20230529
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10219255
DOI: 10.3390/ijms24109095
PMID: 37240439
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms24109095