Estradiol deficiency and skeletal muscle apoptosis : Possible contribution of microRNAs
Karvinen, S., Juppi, H.-K., Le, G., Cabelka, C. A., Mader, T. L., Lowe, D. A., & Laakkonen, E. K. (2021). Estradiol deficiency and skeletal muscle apoptosis : Possible contribution of microRNAs. Experimental Gerontology, 147, Article 111267. https://doi.org/10.1016/j.exger.2021.111267
Published in
Experimental GerontologyAuthors
Date
2021Discipline
LiikuntafysiologiaGerontologia ja kansanterveysGerontologian tutkimuskeskusHyvinvoinnin tutkimuksen yhteisöExercise PhysiologyGerontology and Public HealthGerontology Research CenterSchool of WellbeingCopyright
© 2021 the Authors
Background
Menopause leads to estradiol (E2) deficiency that is associated with decreases in muscle mass and strength. Here we studied the effect of E2 deficiency on miR-signaling that targets apoptotic pathways.
Methods
C57BL6 mice were divided into control (normal estrous cycle, n = 8), OVX (E2 deficiency, n = 7) and OVX + E2 groups (E2-pellet, n = 4). Six weeks following the OVX surgery, mice were sacrificed and RNA isolated from gastrocnemius muscles. miR-profiles were studied with Next-generation sequencing (NGS) and candidate miRs verified using qPCR. The target proteins of the miRs were found using in silico analysis and measured at mRNA (qPCR) and protein levels (Western blot).
Results
Of the apoptosis-linked miRs present, eleven (miRs-92a-3p, 122-5p, 133a-3p, 214-3p, 337-3p, 381-3p, 483-3p, 483-5p, 491-5p, 501-5p and 652-3p) indicated differential expression between OVX and OVX + E2 mice in NGS analysis. In qPCR verification, muscle from OVX mice had lower expression of all eleven miRs compared with OVX + E2 (p < 0.050). Accordingly, OVX had higher expression of cytochrome C and caspases 6 and 9 compared with OVX + E2 at the mRNA level (p < 0.050). At the protein level, OVX also had lower anti-apoptotic BCL-W and greater pro-apoptotic cytochrome C and active caspase 9 compared with OVX + E2 (p < 0.050).
Conclusion
E2 deficiency down regulated several miRs related to apoptotic pathways thus releasing their targets from miR-mediated suppression, which may lead to increased apoptosis and contribute to reduced skeletal muscle mass.
Abbreviations
AIFApoptosis inducing factorBCL2B-cell lymphoma-2 regulator proteinBCL-XLB-cell lymphoma-extra-large regulator proteinBCL-WB-cell lymphoma-like protein 2CASPCaspasecytCCytochrome CE2EstradiolFasLFas ligandGAPDHGlyceraldehyde 3-phosphate dehydrogenaseHSPHeat shock proteinmiRmicroRNANGSNext-generation sequencingOVXOvariectomy
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Publisher
ElsevierISSN Search the Publication Forum
0531-5565Keywords
Dataset(s) related to the publication
Laakkonen, Eija; Kovanen, Vuokko; Sipilä, Sarianna. (2022). Data from Estrogenic Regulation of Muscle Apoptosis (ERMA) study. University of Jyväskylä. https://doi.org/10.17011/jyx/dataset/83491. https://urn.fi/URN:NBN:fi:jyu-202210074820Publication in research information system
https://converis.jyu.fi/converis/portal/detail/Publication/51413289
Metadata
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- Liikuntatieteiden tiedekunta [3157]
Related funder(s)
Research Council of FinlandFunding program(s)
Academy Research Fellow, AoF; Research costs of Academy Research Fellow, AoFAdditional information about funding
This project was funded by the Academy of Finland (grants 309504, 314181 and 335249 to EKL) and NIH grants R01 AG031743 and R01 AG062899 (to DAL). GL was supported by T32 AR050938, CAC by T32 AR007612, and TLM by T32 AG029796License
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