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The Effect of Sirtuin 1 Inhibitor Ex-527 and Activator Resveratrol on the Oocytes’ Cells Viability in Mice Model of Experimental Systemic Autoimmune Damage

Received: 26 October 2021    Accepted: 22 November 2021    Published: 29 November 2021
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Abstract

Introduction: Female infertility is a very common pathology for women of reproductive age with autoimmune disorders, which are known to be followed by the abnormal increment of reactive oxygen species levels, moreover, further contributing to follicular atresia and aging of oocytes in the ovaries what directly leads to infertility. Thus, in search for strategies of preventing oxidative threat to ovaries, the current study was aimed to assess the influence of sirtuin 1, a key cellular metabolism regulator and oxidative stress, activator/blocker on the viability of the follicular environment of oocytes (FEO) cells under conditions of experimental systemic autoimmune damage (ESAD). Methods: The study was performed using the model of ESAD on female mice. The FEO cells were cultivated in different conditions: resveratrol 20 µM, Ex-527 20 µM. After 24h, the cells were examined for viability; the ways of cell death via apoptosis, necrosis were estimated using the method of in vivo dual-color with fluorescent nucleic acid dyes Hoechst 33342 and propidium iodide, and the levels of autophagy were estimated using the autophagic vacuoles labeling with monodansylcadaverine assay. Results: The obtained data indicate that a specific inhibitor of sirtuin 1 Ex-527 (20 µM) in vitro inhibits the viability of cells of the FEO cells and increases the percent of cell death via autophagy, apoptosis, and necrosis. On the contrary, the activator of sirtuin 1 - resveratrol, led to an improvement of the viability status of FEO cells, while reducing the negative impact of the inflammatory process. Unidirectional action of Ex-527 and resveratrol compounds at the cellular level has been established. Conclusion: Thus, the results of the present study suggest the involvement of sirtuin 1 in the regulation of the damaging effect of reactive oxygen species on female ovarian cells under the conditions of experimental systemic autoimmune damage.

Published in Advances in Applied Physiology (Volume 6, Issue 2)
DOI 10.11648/j.aap.20210602.15
Page(s) 47-52
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This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Ovarian Cells, Autophagy, Apoptosis, Sirtuins, Resveratrol, Ex-527, Systemic Autoimmune Damage

References
[1] Chen, Z., Shentu, T. P., Wen, L., Johnson, D. A., & Shyy, J. Y. (2013). Regulation of SIRT1 by oxidative stress-responsive miRNAs and a systematic approach to identify its role in the endothelium. Antioxidants & redox signaling, 19 (13), 1522–1538. https://doi.org/10.1089/ars.2012.4803.
[2] Chen, Z., Kang, X., Wang, L., Dong, H., Wang, C., Xiong, Z., Zhao, W., Jia, C., Lin, J., Zhang, W., Yuan, W., Zhong, M., Du, H., & Bai, X. (2015). Rictor/mTORC2 pathway in oocytes regulates folliculogenesis, and its inactivation causes premature ovarian failure. The Journal of biological chemistry, 290 (10), 6387–6396. https://doi.org/10.1074/jbc.M114.605261.
[3] Gilbert S, Weiner D, Gipson D. National Kidney Foundation’s Primer on Kidney Diseases, 6th edition. Elselvier. 2014; 592.
[4] Khizroeva, J., Nalli, C., Bitsadze, V., Lojacono, A., Zatti, S., Andreoli, L., Tincani, A., Shoenfeld, Y., & Makatsariya, A. (2019). Infertility in women with systemic autoimmune diseases. Best practice & research. Clinical endocrinology & metabolism, 33 (6), 101369. https://doi.org/10.1016/j.beem.2019.101369.
[5] Ronco, P., & Debiec, H. (2012). Pathogenesis of membranous nephropathy: recent advances and future challenges. Nature reviews. Nephrology, 8 (4), 203–213. https://doi.org/10.1038/nrneph.2012.35.
[6] Rives, N., Verhaeghe, F., Di Pizio, P., & Rives, A. (2018). Préservation de la fertilité [Fertility preservation]. La Revue du praticien, 68 (2), 213–219.
[7] Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., Gargiulo, G., Testa, G., Cacciatore, F., Bonaduce, D., & Abete, P. (2018). Oxidative stress, aging, and diseases. Clinical interventions in aging, 13, 757–772. https://doi.org/10.2147/CIA.S158513.
[8] Takeo, S., Sato, D., Kimura, K., Monji, Y., Kuwayama, T., Kawahara-Miki, R., & Iwata, H. (2014). Resveratrol improves the mitochondrial function and fertilization outcome of bovine oocytes. The Journal of reproduction and development, 60 (2), 92–99. https://doi.org/10.1262/jrd.2013-102Team, C. F. (2020). Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) - United States, February 12-March 16, 2020. MMWR. Morbidity and mortality weekly report, 69 12, 343-346.
[9] Li, Y., Dai, D., Lu, Q., Fei, M., Li, M., & Wu, X. (2013). Sirt2 suppresses glioma cell growth through targeting NF-κB-miR-21 axis. Biochemical and biophysical research communications, 441 (3), 661–667. https://doi.org/10.1016/j.bbrc.2013.10.077.
[10] Tatone C, Di Emidio G, Barbonetti A, Carta G, Luciano AM, Falone S, et al. Sirtuins in gamete biology and reproductive physiology: emerging roles and therapeutic potential in female and male infertility. Hum Reprod Update. 2018 May 1; 24 (3): 267-289. doi: 10.1093/humupd/dmy003.
[11] Fu, H., Wada-Hiraike, O., Hirano, M., Kawamura, Y., Sakurabashi, A., Shirane, A., Morita, Y., Isono, W., Oishi, H., Koga, K., Oda, K., Kawana, K., Yano, T., Kurihara, H., Osuga, Y., & Fujii, T. (2014). SIRT3 positively regulates the expression of folliculogenesis- and luteinization-related genes and progesterone secretion by manipulating oxidative stress in human luteinized granulosa cells. Endocrinology, 155 (8), 3079–3087. https://doi.org/10.1210/en.2014-1025.
[12] Gertz, M., Fischer, F., Nguyen, G. T., Lakshminarasimhan, M., Schutkowski, M., Weyand, M., & Steegborn, C. (2013). Ex-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism. Proceedings of the National Academy of Sciences of the United States of America, 110 (30), E2772–E2781. https://doi.org/10.1073/pnas.1303628110.
[13] Tatone, C., Di Emidio, G., Vitti, M., Di Carlo, M., Santini, S., Jr, D'Alessandro, A. M., Falone, S., & Amicarelli, F. (2015). Sirtuin Functions in Female Fertility: Possible Role in Oxidative Stress and Aging. Oxidative medicine and cellular longevity, 2015, 659687. https://doi.org/10.1155/2015/659687.
[14] Tatone, C., Di Emidio, G., Barbonetti, A., Carta, G., Luciano, A. M., Falone, S., & Amicarelli, F. (2018). Sirtuins in gamete biology and reproductive physiology: emerging roles and therapeutic potential in female and male infertility. Human reproduction update, 24 (3), 267–289. https://doi.org/10.1093/humupd/dmy003.
[15] Weng Q, Liu Z, Li B, Liu K, Wu W, Liu H (2016) Oxidative Stress Induces Mouse Follicular Granulosa Cells Apoptosis via JNK/FoxO1 Pathway. PLoS ONE 11 (12): e0167869. https://doi.org/10.1371/journal.pone.0167869.
[16] Zhou, X. L., Xu, J. J., Ni, Y. H., Chen, X. C., Zhang, H. X., Zhang, X. M., Liu, W. J., Luo, L. L., & Fu, Y. C. (2014). SIRT1 activator (SRT1720) improves the follicle reserve and prolongs the ovarian lifespan of diet-induced obesity in female mice via activating SIRT1 and suppressing mTOR signaling. Journal of ovarian research, 7, 97. https://doi.org/10.1186/s13048-014-0097-z.
[17] Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, et al. (2012) Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ.107-20. doi: 10.1038/cdd.2011.96.
[18] Hochreiter-Hufford, A., & Ravichandran, K. S. (2013). Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion. Cold Spring Harbor perspectives in biology, 5 (1), a008748. https://doi.org/10.1101/cshperspect.a008748.
[19] Sirotkin, A. V., Kardošová, D., Alwasel, S. H., & Harrath, A. H. (2015). Neuropeptide Y directly affects ovarian cell proliferation and apoptosis. Reproductive biology, 15 (4), 257–260. https://doi.org/10.1016/j.repbio.2015.07.004.
[20] Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P et al. (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 25 (3): 486-541. doi: 10.1038/s41418-017-0012-4.
[21] Janssen, W. J., & Henson, P. M. (2012). Cellular regulation of the inflammatory response. Toxicologic pathology, 40 (2), 166–173. https://doi.org/10.1177/0192623311428477.
[22] Kolb, J. P., Oguin, T. H., 3rd, Oberst, A., & Martinez, J. (2017). Programmed Cell Death and Inflammation: Winter Is Coming. Trends in immunology, 38 (10), 705–718. https://doi.org/10.1016/j.it.2017.06.009.
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    Mariia Stupchuk, Alina Lytvynenko, Tetyana Voznesenska. (2021). The Effect of Sirtuin 1 Inhibitor Ex-527 and Activator Resveratrol on the Oocytes’ Cells Viability in Mice Model of Experimental Systemic Autoimmune Damage. Advances in Applied Physiology, 6(2), 47-52. https://doi.org/10.11648/j.aap.20210602.15

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    Mariia Stupchuk; Alina Lytvynenko; Tetyana Voznesenska. The Effect of Sirtuin 1 Inhibitor Ex-527 and Activator Resveratrol on the Oocytes’ Cells Viability in Mice Model of Experimental Systemic Autoimmune Damage. Adv. Appl. Physiol. 2021, 6(2), 47-52. doi: 10.11648/j.aap.20210602.15

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    AMA Style

    Mariia Stupchuk, Alina Lytvynenko, Tetyana Voznesenska. The Effect of Sirtuin 1 Inhibitor Ex-527 and Activator Resveratrol on the Oocytes’ Cells Viability in Mice Model of Experimental Systemic Autoimmune Damage. Adv Appl Physiol. 2021;6(2):47-52. doi: 10.11648/j.aap.20210602.15

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  • @article{10.11648/j.aap.20210602.15,
      author = {Mariia Stupchuk and Alina Lytvynenko and Tetyana Voznesenska},
      title = {The Effect of Sirtuin 1 Inhibitor Ex-527 and Activator Resveratrol on the Oocytes’ Cells Viability in Mice Model of Experimental Systemic Autoimmune Damage},
      journal = {Advances in Applied Physiology},
      volume = {6},
      number = {2},
      pages = {47-52},
      doi = {10.11648/j.aap.20210602.15},
      url = {https://doi.org/10.11648/j.aap.20210602.15},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.aap.20210602.15},
      abstract = {Introduction: Female infertility is a very common pathology for women of reproductive age with autoimmune disorders, which are known to be followed by the abnormal increment of reactive oxygen species levels, moreover, further contributing to follicular atresia and aging of oocytes in the ovaries what directly leads to infertility. Thus, in search for strategies of preventing oxidative threat to ovaries, the current study was aimed to assess the influence of sirtuin 1, a key cellular metabolism regulator and oxidative stress, activator/blocker on the viability of the follicular environment of oocytes (FEO) cells under conditions of experimental systemic autoimmune damage (ESAD). Methods: The study was performed using the model of ESAD on female mice. The FEO cells were cultivated in different conditions: resveratrol 20 µM, Ex-527 20 µM. After 24h, the cells were examined for viability; the ways of cell death via apoptosis, necrosis were estimated using the method of in vivo dual-color with fluorescent nucleic acid dyes Hoechst 33342 and propidium iodide, and the levels of autophagy were estimated using the autophagic vacuoles labeling with monodansylcadaverine assay. Results: The obtained data indicate that a specific inhibitor of sirtuin 1 Ex-527 (20 µM) in vitro inhibits the viability of cells of the FEO cells and increases the percent of cell death via autophagy, apoptosis, and necrosis. On the contrary, the activator of sirtuin 1 - resveratrol, led to an improvement of the viability status of FEO cells, while reducing the negative impact of the inflammatory process. Unidirectional action of Ex-527 and resveratrol compounds at the cellular level has been established. Conclusion: Thus, the results of the present study suggest the involvement of sirtuin 1 in the regulation of the damaging effect of reactive oxygen species on female ovarian cells under the conditions of experimental systemic autoimmune damage.},
     year = {2021}
    }
    

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  • TY  - JOUR
    T1  - The Effect of Sirtuin 1 Inhibitor Ex-527 and Activator Resveratrol on the Oocytes’ Cells Viability in Mice Model of Experimental Systemic Autoimmune Damage
    AU  - Mariia Stupchuk
    AU  - Alina Lytvynenko
    AU  - Tetyana Voznesenska
    Y1  - 2021/11/29
    PY  - 2021
    N1  - https://doi.org/10.11648/j.aap.20210602.15
    DO  - 10.11648/j.aap.20210602.15
    T2  - Advances in Applied Physiology
    JF  - Advances in Applied Physiology
    JO  - Advances in Applied Physiology
    SP  - 47
    EP  - 52
    PB  - Science Publishing Group
    SN  - 2471-9714
    UR  - https://doi.org/10.11648/j.aap.20210602.15
    AB  - Introduction: Female infertility is a very common pathology for women of reproductive age with autoimmune disorders, which are known to be followed by the abnormal increment of reactive oxygen species levels, moreover, further contributing to follicular atresia and aging of oocytes in the ovaries what directly leads to infertility. Thus, in search for strategies of preventing oxidative threat to ovaries, the current study was aimed to assess the influence of sirtuin 1, a key cellular metabolism regulator and oxidative stress, activator/blocker on the viability of the follicular environment of oocytes (FEO) cells under conditions of experimental systemic autoimmune damage (ESAD). Methods: The study was performed using the model of ESAD on female mice. The FEO cells were cultivated in different conditions: resveratrol 20 µM, Ex-527 20 µM. After 24h, the cells were examined for viability; the ways of cell death via apoptosis, necrosis were estimated using the method of in vivo dual-color with fluorescent nucleic acid dyes Hoechst 33342 and propidium iodide, and the levels of autophagy were estimated using the autophagic vacuoles labeling with monodansylcadaverine assay. Results: The obtained data indicate that a specific inhibitor of sirtuin 1 Ex-527 (20 µM) in vitro inhibits the viability of cells of the FEO cells and increases the percent of cell death via autophagy, apoptosis, and necrosis. On the contrary, the activator of sirtuin 1 - resveratrol, led to an improvement of the viability status of FEO cells, while reducing the negative impact of the inflammatory process. Unidirectional action of Ex-527 and resveratrol compounds at the cellular level has been established. Conclusion: Thus, the results of the present study suggest the involvement of sirtuin 1 in the regulation of the damaging effect of reactive oxygen species on female ovarian cells under the conditions of experimental systemic autoimmune damage.
    VL  - 6
    IS  - 2
    ER  - 

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Author Information
  • Department of Immunophysiology, Bogomoletz Institute of Physiology of National Academy of Sciences of Ukraine, Kyiv, Ukraine

  • Department of Immunophysiology, Bogomoletz Institute of Physiology of National Academy of Sciences of Ukraine, Kyiv, Ukraine

  • Department of Immunophysiology, Bogomoletz Institute of Physiology of National Academy of Sciences of Ukraine, Kyiv, Ukraine

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