اخبار و اعلانات

 آمار

تعداد نشریات31
تعداد شماره‌ها834
تعداد مقالات8,015
تعداد مشاهده مقاله14,852,484
تعداد دریافت فایل اصل مقاله9,586,508
Jabari, Ayob, Salahi, Elnaz. (1405). Mitochondria‑targeted antioxidant MitoQ10 ameliorates p-ASK1 and TRAF2/6 in PCOS mouse model. نشریه علمی دانشگاه سیستان و بلوچستان, 7(1), 15-20. doi: 10.22111/jep.2026.53949.1101
Ayob Jabari; Elnaz Salahi. "Mitochondria‑targeted antioxidant MitoQ10 ameliorates p-ASK1 and TRAF2/6 in PCOS mouse model". نشریه علمی دانشگاه سیستان و بلوچستان, 7, 1, 1405, 15-20. doi: 10.22111/jep.2026.53949.1101
Jabari, Ayob, Salahi, Elnaz. (1405). 'Mitochondria‑targeted antioxidant MitoQ10 ameliorates p-ASK1 and TRAF2/6 in PCOS mouse model', نشریه علمی دانشگاه سیستان و بلوچستان, 7(1), pp. 15-20. doi: 10.22111/jep.2026.53949.1101
Jabari, Ayob, Salahi, Elnaz. Mitochondria‑targeted antioxidant MitoQ10 ameliorates p-ASK1 and TRAF2/6 in PCOS mouse model. نشریه علمی دانشگاه سیستان و بلوچستان, 1405; 7(1): 15-20. doi: 10.22111/jep.2026.53949.1101

Mitochondria‑targeted antioxidant MitoQ10 ameliorates p-ASK1 and TRAF2/6 in PCOS mouse model

Journal of Epigenetics
دوره 7، شماره 1، تیر 2026، صفحه 15-20    اصل مقاله (588.56 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22111/jep.2026.53949.1101
نویسندگان
Ayob Jabari1؛ Elnaz Salahi* 2
1Department of Obstetrics and Gynecology, Molud Infertility Center, Zahedan University of Medical Sciences, Zahedan, Iran.
2Department of Obstetrics and Gynecology, Molud Infertility Center, Zahedan University of Medical Sciences, Zahedan, Iran.
چکیده
Mitochondrial dysfunction and the resulting oxidative stress have been increasingly recognized as playing a significant role in the development and progression of polycystic ovary syndrome (PCOS), which is the most prevalent endocrine disorder affecting women during their reproductive years. This study was designed to explore the potential therapeutic effects of MitoQ10, a novel antioxidant specifically targeted to the mitochondria, on mitochondrial function and oxidative stress markers in a mouse model of PCOS.
We focused on examining the expression levels of phosphorylated apoptosis signal-regulating kinase 1 (p-ASK1) and tumor necrosis factor receptor-associated factors 2 and 6 (TRAF2/6) in granulosa cells (GCs) obtained from a dehydroepiandrosterone (DHEA)-induced PCOS mouse model by Real-Time PCR and Western blot. Female BALB/c mice were randomly assigned to one of three experimental groups: a Control group, a PCOS group induced by DHEA, and a PCOS + MitoQ10 (500 μmol/L) group. All groups were treated for a duration of 21 days.
The results of our study revealed that the expression levels of p-ASK1, TRAF2, and TRAF6 were significantly elevated in the PCOS group compared to the control group, indicating increased oxidative stress and inflammatory signaling in the PCOS model. Importantly, treatment with MitoQ10 resulted in a downregulation of these elevated expression levels (p ˂ 0.05), suggesting a mitigating effect of MitoQ10 on oxidative stress. However, it was noted that TRAF6 gene expression did not show a statistically significant difference between the MitoQ10-treated group and the PCOS group, indicating a potentially more complex regulatory mechanism for TRAF6.
In conclusion, these preliminary findings provide evidence suggesting that MitoQ10, a readily available dietary supplement, holds promise as a potential effective adjunct in the treatment of PCOS. The observed beneficial effects warrant further investigation through properly designed clinical trials.
کلیدواژه‌ها
PCOS؛ DHEA؛ MitoQ10؛ p-ASK1؛ TRAF2/6؛ Oxidative Stress
مراجع
  1. Lu J, Wang Z, Cao J, Chen Y, Dong Y. A novel and compact review on the role of oxidative stress in female reproduction. Reproductive Biology and Endocrinology. 2018;16:1-18.
  2. Benrick A, Chanclón B, Micallef P, Wu Y, Hadi L, Shelton JM, et al. Adiponectin protects against development of metabolic disturbances in a PCOS mouse model. Proceedings of the National Academy of Sciences. 2017;114(34):E7187-E96.
  3. Agarwal A, Gupta S. Role of reactive oxygen species in female reproduction. Part I. Oxidative stress: a general overview. Women Health. 2005;1(21):5.
  4. Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reproductive biology and endocrinology. 2012;10:1-31.
  5. Fujii J, Iuchi Y, Okada F. Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system. Reproductive biology and endocrinology. 2005;3(1):1-10.
  6. Wu J, Wu Y, Zhang X, Li S, Lu D, Li S, et al. Elevated serum thioredoxin‐interacting protein in women with polycystic ovary syndrome is associated with insulin resistance. Clinical endocrinology. 2014;80(4):538-44.
  7. Yavuz S, Aydin NE, Celik O, Yilmaz E, Ozerol E, Tanbek K. Resveratrol successfully treats experimental endometriosis through modulation of oxidative stress and lipid peroxidation. Journal of cancer research and therapeutics. 2014;10(2):324-9.
  8. Sohel MMH, Amin A, Prastowo S, Linares-Otoya L, Hoelker M, Schellander K, et al. Sulforaphane protects granulosa cells against oxidative stress via activation of NRF2-ARE pathway. Cell and tissue research. 2018;374:629-41.
  9. Sugiura K, Pendola FL, Eppig JJ. Oocyte control of metabolic cooperativity between oocytes and companion granulosa cells: energy metabolism. Developmental biology. 2005;279(1):20-30.
  10. Wang R-S, Chang H-Y, Kao S-H, Kao C-H, Wu Y-C, Yeh S, et al. Abnormal mitochondrial function and impaired granulosa cell differentiation in androgen receptor knockout mice. International journal of molecular sciences. 2015;16(5):9831-49.
  11. Braakhuis AJ, Nagulan R, Somerville V. The effect of MitoQ on aging-related biomarkers: a systematic review and meta-analysis. Oxidative medicine and cellular longevity. 2018;2018.
  12. Williamson J, Hughes CM, Cobley JN, Davison GW. The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage. Redox biology. 2020;36:101673.
  13. Salahi E, Amidi F, Zahiri Z, Aghahosseini M, Mashayekhi F, Amani Abkenari S, et al. The effect of mitochondria-targeted antioxidant MitoQ10 on redox signaling pathway components in PCOS mouse model. Archives of gynecology and obstetrics. 2022:1-10.
  14. Fujino G, Noguchi T, Takeda K, Ichijo H, editors. Thioredoxin and protein kinases in redox signaling. Seminars in cancer biology; 2006: Elsevier.
  15. Lee S, Kim SM, Lee RT. Thioredoxin and thioredoxin target proteins: from molecular mechanisms to functional significance. Antioxidants & redox signaling. 2013;18(10):1165-207.
  16. Ding Y, Jiang Z, Xia B, Zhang L, Zhang C, Leng J. Mitochondria-targeted antioxidant therapy for an animal model of PCOS-IR. International journal of molecular medicine. 2019;43(1):316-24.
  17. Liu T, Zhou HJ, Min W. ASK family in cardiovascular biology and medicine. Advances in biological regulation. 2017;66:54-62.
  18. Sayama K, Hanakawa Y, Shirakata Y, Yamasaki K, Sawada Y, Sun L, et al. Apoptosis signal-regulating kinase 1 (ASK1) is an intracellular inducer of keratinocyte differentiation. Journal of Biological Chemistry. 2001;276(2):999-1004.
  19. Sirotkin AV, Petrak J, Alwasel S, Harrath AH. Apoptosis signal-regulating kinase (ASK1) and transcription factor tumor suppressor protein TP53 suppress rabbit ovarian granulosa cell functions. Animal reproduction science. 2019;204:140-51.
  20. Yin M, Zhou HJ, Zhang J, Lin C, Li H, Li X, et al. ASK1-dependent endothelial cell activation is critical in ovarian cancer growth and metastasis. JCI insight. 2017;2(18).
  21. Victor VM, Rovira-Llopis S, Banuls C, Diaz-Morales N, Martinez de Maranon A, Rios-Navarro C, et al. Insulin resistance in PCOS patients enhances oxidative stress and leukocyte adhesion: role of myeloperoxidase. PLoS One. 2016;11(3):e0151960.
  22. Blair SA, Kyaw-Tun T, Young IS, Phelan NA, Gibney J, McEneny J. Oxidative stress and inflammation in lean and obese subjects with polycystic ovary syndrome. The Journal of reproductive medicine. 2013;58(3-4):107-14.
  23. Gane EJ, Weilert F, Orr DW, Keogh GF, Gibson M, Lockhart MM, et al. The mitochondria‐targeted anti‐oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients. Liver international. 2010;30(7):1019-26.
  24. James AM, Sharpley MS, Manas A-RB, Frerman FE, Hirst J, Smith RA, et al. Interaction of the mitochondria-targeted antioxidant MitoQ with phospholipid bilayers and ubiquinone oxidoreductases. Journal of Biological Chemistry. 2007;282(20):14708-18.
  25. Siegmund D, Wagner J, Wajant H. TNF Receptor Associated Factor 2 (TRAF2) Signaling in Cancer. Cancers. 2022;14(16):4055.
  26. Li J, Liu N, Tang L, Yan B, Chen X, Zhang J, et al. The relationship between TRAF6 and tumors. Cancer Cell International. 2020;20:1-12.
  27. Gissler MC, Stachon P, Wolf D, Marchini T. The role of tumor necrosis factor Associated factors (TRAFs) in vascular inflammation and atherosclerosis. Frontiers in Cardiovascular Medicine. 2022;9.
  28. Lim R, Barker G, Lappas M. TRADD, TRAF 2, RIP 1 and TAK 1 are required for TNF‐α‐induced pro‐labour mediators in human primary myometrial cells. American Journal of Reproductive Immunology. 2017;78(1):e12664.
  29. Yoshikawa M, Iriyama T, Suzuki K, Sayama S, Tsuruga T, Kumasawa K, et al. ASK1 promotes uterine inflammation leading to pathological preterm birth. Scientific Reports. 2020;10(1):1887.
آمار
تعداد مشاهده مقاله: 73
تعداد دریافت فایل اصل مقاله: 10


سامانه مدیریت نشریات علمی. طراحی و پیاده سازی از سیناوب