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 inExperimental Gerontology
DisciplineLiikuntafysiologiaGerontologia ja kansanterveysGerontologian tutkimuskeskusExercise PhysiologyGerontology and Public HealthGerontology Research Center
© 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 ...
Publication in research information system
MetadataShow full item record
- Liikuntatieteiden tiedekunta 
Related funder(s)Academy of Finland
Funding program(s)Research post as Academy Research Fellow, AoF; Research costs of Academy Research Fellow, AoF
Additional information about fundingThis 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 AG029796
Showing items with similar title or keywords.
Associations of resting and peak fat oxidation with sex hormone profile and blood glucose control in middle-aged women Karppinen, Jari E.; Juppi, Hanna-Kaarina; Hintikka, Jukka; Wiklund, Petri; Haapala, Eero A.; Hyvärinen, Matti; Tammelin, Tuija H.; Aukee, Pauliina; Kujala, Urho M.; Laukkanen, Jari; Laakkonen, Eija K. (Elsevier, 2022)Background and Aims Menopause may reduce fat oxidation. We investigated whether sex hormone profile explains resting fat oxidation (RFO) or peak fat oxidation (PFO) during incremental cycling in middle-aged women. ...
Aging and microRNA messaging : associations with systemic estrogen levels and physical performance Kangas, Reeta (University of Jyväskylä, 2018)This thesis took an innovative approach, which involved methodological development, to investigate microRNAs as candidate molecules and as genome-wide regulators of age, menopausal status and physical condition in both ...
Design and protocol of Estrogenic Regulation of Muscle Apoptosis (ERMA) study with 47 to 55-year-old women's cohort : novel results show menopause-related differences in blood count Kovanen, Vuokko; Aukee, Pauliina; Kokko, Katja; Finni Juutinen, Taija; Tarkka, Ina; Tammelin, Tuija; Kujala, Urho; Sipilä, Sarianna; Laakkonen, Eija (Lippincott Williams & Wilkins, 2018)Objective: The multidisciplinary Estrogenic Regulation of Muscle Apoptosis (ERMA) study was designed to reveal how hormonal differences over the menopausal stages affect the physiological and psychological functioning ...
Karppinen, Jari E.; Törmäkangas, Timo; Kujala, Urho M.; Sipilä, Sarianna; Laukkanen, Jari; Aukee, Pauliina; Kovanen, Vuokko; Laakkonen, Eija K. (Oxford University Press (OUP), 2022)Aims We studied the changes in the circulating metabolome and their relation to the menopausal hormonal shift in 17β-oestradiol and follicle-stimulating hormone levels among women transitioning from perimenopause to early ...
Dalgaard, Line B.; Dalgas, Ulrik; Andersen, Jesper L.; Rossen, Nicklas B.; Møller, Andreas Buch; Stødkilde-Jørgensen, Hans; Jørgensen, Jens Otto; Kovanen, Vuokko; Couppé, Christian; Langberg, Henning; Kjær, Michael; Hansen, Mette (Frontiers Media, 2019)Introduction: The majority of young women use oral contraceptives (OCs). Use of OCs has been associated with lower myofibrillar protein and tendon collagen synthesis rates, but it is unknown whether OCs will limit the ...