دورية أكاديمية
Transcriptomic Analysis of the Effect of Torin-2 on the Central Nervous System of Drosophila melanogaster .
العنوان: | Transcriptomic Analysis of the Effect of Torin-2 on the Central Nervous System of Drosophila melanogaster . |
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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. |
References: | Brain Behav. 2012 May;2(3):345-56. (PMID: 22741103) Biochim Biophys Acta. 2009 Oct;1790(10):1067-74. (PMID: 19539012) J Cell Biol. 2001 Jul 23;154(2):267-73. (PMID: 11470816) Bioinformatics. 2010 Jan 1;26(1):139-40. (PMID: 19910308) Int J Mol Sci. 2018 Mar 16;19(3):. (PMID: 29547541) Science. 2009 Jul 10;325(5937):201-4. (PMID: 19590001) Mech Ageing Dev. 2004 Sep;125(9):629-32. (PMID: 15491681) Life Sci. 2007 Aug 9;81(9):740-9. (PMID: 17698151) Int J Med Sci. 2021 Jan 1;18(1):137-149. (PMID: 33390782) Front Neurosci. 2017 Apr 06;11:185. (PMID: 28428740) Trends Endocrinol Metab. 2018 Nov;29(11):737-739. (PMID: 30082207) J Vet Emerg Crit Care (San Antonio). 2022 Nov;32(6):756-763. (PMID: 35522236) Bioinformatics. 2012 Aug 15;28(16):2184-5. (PMID: 22743226) Curr Biol. 2004 May 25;14(10):885-90. (PMID: 15186745) Science. 2002 Apr 12;296(5566):319. (PMID: 11951037) Exp Gerontol. 2015 Aug;68:51-8. (PMID: 25481271) Shock. 2000 Aug;14(2):81-90. (PMID: 10947147) Annu Rev Med. 2017 Jan 14;68:413-430. (PMID: 28099083) Cells. 2021 Jun 29;10(7):. (PMID: 34210082) OMICS. 2012 May;16(5):284-7. (PMID: 22455463) J Cell Mol Med. 2008 Oct;12(5B):1872-84. (PMID: 18363840) Endocrinology. 2021 Nov 1;162(11):. (PMID: 34467976) Biochim Biophys Acta. 2008 Jan;1784(1):116-32. (PMID: 17913600) Dis Model Mech. 2023 Apr 1;16(4):. (PMID: 36847474) Glia. 2006 Mar;53(4):401-11. (PMID: 16342169) Genetica. 1993;91(1-3):89-98. (PMID: 8125281) Neuron. 2009 Jan 15;61(1):10-26. (PMID: 19146809) PLoS One. 2014 Mar 14;9(3):e91851. (PMID: 24632678) Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12610-5. (PMID: 15308776) J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2016 Jun;202(6):399-409. (PMID: 27138222) Biochim Biophys Acta Proteins Proteom. 2021 Jan;1869(1):140542. (PMID: 32950692) Cell Cycle. 2010 Feb 15;9(4):683-8. (PMID: 20139716) J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2014 Apr;200(4):251-64. (PMID: 24567257) Cell. 2018 Jan 25;172(3):590-604.e13. (PMID: 29373831) Neural Regen Res. 2021 Mar;16(3):498-499. (PMID: 32985472) G3 (Bethesda). 2019 Dec 3;9(12):4197-4207. (PMID: 31624139) Sci Rep. 2019 Jun 24;9(1):9151. (PMID: 31235842) Science. 2001 Apr 6;292(5514):107-10. (PMID: 11292875) J Neurosci Methods. 2002 Jan 15;113(1):99-110. (PMID: 11741727) Aging (Albany NY). 2012 Nov;4(11):768-89. (PMID: 23211361) J Neurosci. 2006 Aug 2;26(31):8048-56. (PMID: 16885218) Cell Stress Chaperones. 2020 Mar;25(2):305-315. (PMID: 32040825) J Clin Invest. 2013 Mar;123(3):980-9. (PMID: 23454761) Cell Mol Life Sci. 2014 Nov;71(22):4325-46. (PMID: 25015322) Nature. 2013 Jan 17;493(7432):338-45. (PMID: 23325216) J Biol Chem. 2003 Aug 15;278(33):31033-42. (PMID: 12788951) Cell. 2006 Oct 6;127(1):49-58. (PMID: 17018276) Oncotarget. 2016 Aug 30;7(35):56147-56152. (PMID: 27528229) Cell Tissue Res. 2021 Mar;383(3):931-947. (PMID: 33409654) Behav Brain Res. 2004 May 5;151(1-2):219-24. (PMID: 15084438) Glia. 2017 Sep;65(9):1504-1520. (PMID: 28618077) Semin Cell Dev Biol. 2003 Oct;14(5):291-9. (PMID: 14986859) J Cell Physiol. 2012 Mar;227(3):1235-41. (PMID: 21688267) Trends Genet. 2004 Aug;20(8):384-91. (PMID: 15262411) Science. 2001 Apr 6;292(5514):104-6. (PMID: 11292874) J Neurosci Res. 2004 Aug 15;77(4):540-51. (PMID: 15264224) Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886) Cell Metab. 2014 Mar 4;19(3):373-9. (PMID: 24508508) Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):E9899-E9908. (PMID: 30275300) Curr Opin Immunol. 2020 Feb;62:22-30. (PMID: 31835066) Rev Neurosci. 2005;16(2):137-49. (PMID: 15957577) Mol Cell Endocrinol. 2009 Feb 5;299(1):39-50. (PMID: 18682271) Exp Gerontol. 2011 May;46(5):376-81. (PMID: 20849947) Science. 2007 Feb 23;315(5815):1133-7. (PMID: 17272684) Cell. 2018 Aug 9;174(4):982-998.e20. (PMID: 29909982) Cell. 2017 Apr 6;169(2):361-371. (PMID: 28388417) J Gerontol A Biol Sci Med Sci. 2000 Nov;55(11):B552-9. (PMID: 11078089) Int J Neurosci. 2019 Feb;129(2):179-188. (PMID: 29962282) Cell Rep. 2018 Jun 19;23(12):3501-3511. (PMID: 29924994) Trends Neurosci. 2010 Feb;33(2):67-75. (PMID: 19963289) F1000Res. 2018 Feb 7;7:160. (PMID: 29487742) Curr Alzheimer Res. 2022;19(7):494-502. (PMID: 35929621) Exp Gerontol. 2011 May;46(5):349-54. (PMID: 21111799) J Pharm Biomed Anal. 2015 Dec 10;116:18-24. (PMID: 25740810) J Gerontol A Biol Sci Med Sci. 2014 Feb;69(2):119-30. (PMID: 23682161) Arch Insect Biochem Physiol. 2018 Aug;98(4):e21464. (PMID: 29637607) Glia. 2005 Oct;52(1):78-84. (PMID: 15920727) Dev Biol. 1999 Mar 1;207(1):107-18. (PMID: 10049568) Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):467-72. (PMID: 11756682) Mol Brain. 2017 Oct 30;10(1):50. (PMID: 29084578) Fly (Austin). 2022 Dec;16(1):152-176. (PMID: 35499154) Behav Brain Res. 2010 Dec 6;214(1):18-24. (PMID: 20478338) PLoS One. 2013 Apr 09;8(4):e60868. (PMID: 23585858) J Neurosci. 2004 Feb 11;24(6):1439-45. (PMID: 14960616) PLoS One. 2012;7(9):e46057. (PMID: 23049932) Cardiovasc Diabetol. 2019 Aug 30;18(1):114. (PMID: 31470858) |
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 |
تدمد: | 1422-0067 |
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DOI: | 10.3390/ijms24109095 |