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THE EFFECT OF COENZYME Q10 ADMINISTRATION ON THE EXPRESSION OF Gdnf, Plzf, Sox3, Thy1 GENES IN RATS WITH HYPOTHYROIDISM

Year 2024, , 129 - 135, 20.08.2024
https://doi.org/10.24938/kutfd.1390539

Abstract

Objective: Hypothyroidism is a problem of deficient production of thyroid hormones. These hormones regulate metabolism. Therefore, the current health status of the person is adversely affected due to thyroid hormone deficiency. Coenzyme Q10 (CoQ10) is a vitamin-like substance with strong antioxidant properties. The aim of this scientific study is to investigate the effects of CoQ10 on hypothyroidism at sera level with important biomarkers glial cell line-derived neurotrophic factor (GDNF), promyelocytic leukaemia zinc finger protein (PLZF), high mobility group box transcription factor 3 (SOX3) and thymocyte differentiation antigen 1 (THY1).
Material and Methods: Four experimental animal groups were formed: Control group (n:7); hypothyroidism group (n:7); CoQ10 group (n:7); hypothyroidism + CoQ10 group (n:7). On the thirty-first day, sera of the animals were collected and Gdnf, Plzf, Sox3, Thy1 expression levels were analyzed in the blood.
Results: Significant results occurred in all four biomarkers. As a final result, both hypothyroid pathology was associated with all biomarkers, and CoQ10 positively affected hypothyroidism.
Conclusion: The effect of coenzyme Q10 on gene expression levels of Plzf, Gdnf, Thy1, Sox3 at sera level in rats with experimental hypothyroidism was shown by molecular analyses. Coenzyme Q10 regulates sera gene expression levels during treatment.

References

  • Almandoz JP, Gharib H. Hypothyroidism: Etiology, diagnosis, and management. Med Clin North Am. 2012;96(2):203-221.
  • Taylor PN, Albrecht D, Scholz A, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. 2018;14(5):301-316.
  • Aktümsek A. Genel Endokrinoloji. 1st edn, Ankara, Nobel Yayınevi, 2020.
  • Schwarz C, Leichtle AB, Arampatzis S, et al. Thyroid function and serum electrolytes: Does an association really exist? Swiss Med Wkly. 2012;142:w13669.
  • Ladenson PW, Singer PA, Ain KB, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med. 2000 Jun 12;160(11):1573- 1575.
  • Giannocco G, Kizys MML, Maciel RM, de Souza JS. Thyroid hormone, gene expression, and central nervous system: Where we are. Semin Cell Dev Biol. 2021;114:47- 56.
  • Schniertshauer D, Müller S, Mayr T, Sonntag T, Gebhard D, Bergemann J. Accelerated regeneration of ATP level after irradiation in human skin fibroblasts by coenzyme Q10. Photochem Photobiol. 2016;92(3):488-494.
  • Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr. 2001;20(6):591-598.
  • Littarru GP, Tiano L. Clinical aspects of coenzyme Q10: An update. Nutrition. 2010;26(3):250-254.
  • Jiang P, Wu M, Zheng Y, et al. Analysis of coenzyme Q(10) in human plasma by column-switching liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;805(2):297-301.
  • Ogura F, Morii H, Ohno M, et al. Serum coenzyme Q10 levels in thyroid disorders. Horm Metab Res. 1980;12(10):537-540.
  • Atkinson Jr AJ, Colburn WA, DeGruttola VG, DeMets DL, Downing GJ, Zeger SL. Biomarkers Definitions Working Group, Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharm Therap. 2001;69(3),89-95.
  • Moulakakis KG, Poulakou MV, Dosios T, et al. Hypothyroidism and the aorta. Evidence of increased oxidative DNA damage to the aorta of hypothyroid rats. In Vivo. 2008;22(5):603-608.
  • Maheshwari R, Balaraman R, Sen AK, Shukla D, Seth A. Effect of concomitant administration of coenzyme Q10 with sitagliptin on experimentally induced diabetic nephropathy in rats. Ren Fail. 2017;39(1):130-139.
  • Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method Methods. 2001;25(4):402- 408.
  • Belluardo N, Mudò G, Caniglia G, et al. Expression of neurotrophins, GDNF, and their receptors in rat thyroid tissue. Cell Tissue Res. 1999;295(3):467-475.
  • Genovese T, Impellizzeri D, Ahmad A, et al. Post- ischaemic thyroid hormone treatment in a rat model of acute stroke. Brain Res. 2013;1513:92-102.
  • Mulligan LM. GDNF and the RET Receptor in cancer: New insights and therapeutic potential. Front Physiol. 2019;9:1873.
  • Han H, Fu X, Zhang Y, Luo D, Zhang X, Wu X. Expression and prognostic value of m6A RNA methylation-related genes in thyroid cancer. Iran J Public Health. 2023;52(9):1902-1916.
  • Bilous II, Korda MM, Krynytska IY, Kamyshnyi AM. Nerve impulse transmission pathway-focused genes expression analysis in patients with primary hypothyroidism and autoimmune thyroiditis. Endocr Regul. 2020;54(2):109-118.
  • Kamyshna II, Pavlovych LB, Kamyshnyi AM. Vitamin D alters the transcriptional profile of blood cells in patients with primary hypothyroidism. Fiziologichnyi Zhurnal (Physiol J). 2022;68(5):16-24.
  • Cockburn JG, Richardson DS, Gujral TS, Mulligan LM. RET-mediated cell adhesion and migration require multiple integrin subunits. J Clin Endocrinol Metab. 2010;95(11):E342-346.
  • Straten G, Eschweiler GW, Maetzler W, Laske C, Leyhe T. Glial cell-line derived neurotrophic factor (GDNF) concentrations in cerebrospinal fluid and serum of patients with early Alzheimer’s disease and normal controls. J Alzheimers Dis. 2009;18(2):331-337.
  • Zhang T, Xiong H, Kan LX, et al. Genomic sequence, structural organization, molecular evolution, and aberrant rearrangement of promyelocytic leukemia zinc finger gene. Proc Natl Acad Sci U S A. 1999;96(20):11422- 11427.
  • Matsuzawa K, Izawa S, Ohkura T, et al. Implication of intracellular localization of transcriptional repressor PLZF in thyroid neoplasms. BMC Endocr Disord. 2014;14:52.
  • Chen X, Huang F, Qi Y, et al. Serum and thyroid tissue level of let-7b and their correlation with TRAb in Graves’ disease. J Transl Med. 2018;5;16(1):188.
  • Stefan M, Wei C, Lombardi A, et al. Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity. Proc Natl Acad Sci USA. 2014;111(34):12562-12567.
  • Rizzoti K, Lovell-Badge R. SOX3 activity during pharyngeal segmentation is required for craniofacial morphogenesis. Development. 2007;134(19):3437-3448.
  • Sun G, Fu L, Wen L, Shi YB. Activation of Sox3 gene by thyroid hormone in the developing adult intestinal stem cell during Xenopus metamorphosis. Endocrinology. 2014;155(12):5024-5032.
  • Huang J, Guo L. Knockdown of SOX9 inhibits the proliferation, invasion, and EMT in thyroid cancer cells. Oncol Res. 2017;25(2):167-176.
  • Endo T, Kobayashi T. Excess TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate. Am J Physiol Endocrinol Metab. 2013;305(5):E660-666.
  • Grimm D, Bauer J, Wise P, et al. The role of SOX family members in solid tumours and metastasis. Semin Cancer Biol. 2020;67(Pt 1):122-153.
  • Li JY, Han C, Zheng LL, Guo MZ. Epigenetic regulation of Wnt signaling pathway gene SRY-related HMG-box 17 in papillary thyroid carcinoma. Chin Med J (Engl). 2012;125(19):3526-3531.
  • Wang L, Shen YF, Shi ZM, Shang XJ, Jin DL, Xi F. Overexpression miR‐211‐5p hinders the proliferation, migration, and invasion of thyroid tumor cells by downregulating SOX 11. J Clin Lab Anal. 2018;32(3):e22293.
  • Horiguchi K, Nakakura T, Yoshida S, et al. Identification of THY1 as a novel thyrotrope marker and THY1 antibody-mediated thyrotrope isolation in the rat anterior pituitary gland. Biochem Biophys Res Commun. 2016;480(2):273-279.
  • Smith TJ, Sempowski GD, Berenson CS, Cao HJ, Wang HS, Phipps RP. Human thyroid fibroblasts exhibit a distinctive phenotype in culture: Characteristic ganglioside profile and functional CD40 expression. Endocrinology. 1997;138(12):5576-5588.
  • Saalbach A, Wetzig T, Haustein UF, Anderegg U. Detection of human soluble Thy-1 in serum by ELISA. Fibroblasts and activated endothelial cells are a possible source of soluble Thy-1 in serum. Cell Tissue Res. 1999;298(2):307-315.

Hipotiroidili Sıçanlarda Koenzim Q10 Uygulamasının Gdnf, Plzf, Sox3, Thy1 Genlerinin İfadesi Üzerine Etkisi

Year 2024, , 129 - 135, 20.08.2024
https://doi.org/10.24938/kutfd.1390539

Abstract

Amaç: Hipotiroidizm, tiroid hormonlarının eksik üretilmesi sorunudur. Bu hormonlar metabolizmayı düzenler. Dolayısıyla tiroid hormon eksikliğine bağlı olarak kişinin mevcut sağlık durumu olumsuz etkilenir. Koenzim Q10 (CoQ10) güçlü antioksidan özelliklere sahip vitamin benzeri bir maddedir. Planlamış olduğumuz bu bilimsel çalışma, CoQ10'un hipotiroidizm üzerine etkilerini, önemli biyobelirteçler olan glial hücre kaynaklı nörotrofik faktör (GDNF), promyelositik lösemi çinko parmağı (PLZF), high mobility group box transcription factor 3 (SOX3) ve timosit farklılaşma antijeni 1 (THY1) ile serum düzeyinde araştırmaktır.
Gereç ve Yöntemler: Dört deney hayvanı grubu oluşturuldu: Kontrol grubu (n:7); hipotiroidi grubu (n:7); CoQ10 grubu (n:7); hipotiroidi + CoQ10 grubu (n:7). Otuz birinci günde hayvanların serumları alındı ve kanda Gdnf, Plzf, Sox3, Thy1 ekspresyon düzeyleri analiz edildi.
Bulgular: Dört biyobelirteçte de anlamlı sonuçlar elde edildi. Nihai sonuç olarak, hem hipotiroid patolojisi tüm bu biyobelirteçlerle ilişkilendirildi hem de CoQ10’un hipotiroidizmi olumlu yönde etkilemiştir.
Sonuç: Deneysel hipotiroidizmli sıçanlarda koenzim Q10'un serum düzeyinde Plzf, Gdnf, Thy1, Sox3'ün gen ifade düzeyinde etkisi moleküler analizlerle gösterilmiştir. Koenzim Q10, tedavi sırasında serum gen ifade seviyelerini düzenlemektedir.

References

  • Almandoz JP, Gharib H. Hypothyroidism: Etiology, diagnosis, and management. Med Clin North Am. 2012;96(2):203-221.
  • Taylor PN, Albrecht D, Scholz A, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. 2018;14(5):301-316.
  • Aktümsek A. Genel Endokrinoloji. 1st edn, Ankara, Nobel Yayınevi, 2020.
  • Schwarz C, Leichtle AB, Arampatzis S, et al. Thyroid function and serum electrolytes: Does an association really exist? Swiss Med Wkly. 2012;142:w13669.
  • Ladenson PW, Singer PA, Ain KB, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med. 2000 Jun 12;160(11):1573- 1575.
  • Giannocco G, Kizys MML, Maciel RM, de Souza JS. Thyroid hormone, gene expression, and central nervous system: Where we are. Semin Cell Dev Biol. 2021;114:47- 56.
  • Schniertshauer D, Müller S, Mayr T, Sonntag T, Gebhard D, Bergemann J. Accelerated regeneration of ATP level after irradiation in human skin fibroblasts by coenzyme Q10. Photochem Photobiol. 2016;92(3):488-494.
  • Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr. 2001;20(6):591-598.
  • Littarru GP, Tiano L. Clinical aspects of coenzyme Q10: An update. Nutrition. 2010;26(3):250-254.
  • Jiang P, Wu M, Zheng Y, et al. Analysis of coenzyme Q(10) in human plasma by column-switching liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;805(2):297-301.
  • Ogura F, Morii H, Ohno M, et al. Serum coenzyme Q10 levels in thyroid disorders. Horm Metab Res. 1980;12(10):537-540.
  • Atkinson Jr AJ, Colburn WA, DeGruttola VG, DeMets DL, Downing GJ, Zeger SL. Biomarkers Definitions Working Group, Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharm Therap. 2001;69(3),89-95.
  • Moulakakis KG, Poulakou MV, Dosios T, et al. Hypothyroidism and the aorta. Evidence of increased oxidative DNA damage to the aorta of hypothyroid rats. In Vivo. 2008;22(5):603-608.
  • Maheshwari R, Balaraman R, Sen AK, Shukla D, Seth A. Effect of concomitant administration of coenzyme Q10 with sitagliptin on experimentally induced diabetic nephropathy in rats. Ren Fail. 2017;39(1):130-139.
  • Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method Methods. 2001;25(4):402- 408.
  • Belluardo N, Mudò G, Caniglia G, et al. Expression of neurotrophins, GDNF, and their receptors in rat thyroid tissue. Cell Tissue Res. 1999;295(3):467-475.
  • Genovese T, Impellizzeri D, Ahmad A, et al. Post- ischaemic thyroid hormone treatment in a rat model of acute stroke. Brain Res. 2013;1513:92-102.
  • Mulligan LM. GDNF and the RET Receptor in cancer: New insights and therapeutic potential. Front Physiol. 2019;9:1873.
  • Han H, Fu X, Zhang Y, Luo D, Zhang X, Wu X. Expression and prognostic value of m6A RNA methylation-related genes in thyroid cancer. Iran J Public Health. 2023;52(9):1902-1916.
  • Bilous II, Korda MM, Krynytska IY, Kamyshnyi AM. Nerve impulse transmission pathway-focused genes expression analysis in patients with primary hypothyroidism and autoimmune thyroiditis. Endocr Regul. 2020;54(2):109-118.
  • Kamyshna II, Pavlovych LB, Kamyshnyi AM. Vitamin D alters the transcriptional profile of blood cells in patients with primary hypothyroidism. Fiziologichnyi Zhurnal (Physiol J). 2022;68(5):16-24.
  • Cockburn JG, Richardson DS, Gujral TS, Mulligan LM. RET-mediated cell adhesion and migration require multiple integrin subunits. J Clin Endocrinol Metab. 2010;95(11):E342-346.
  • Straten G, Eschweiler GW, Maetzler W, Laske C, Leyhe T. Glial cell-line derived neurotrophic factor (GDNF) concentrations in cerebrospinal fluid and serum of patients with early Alzheimer’s disease and normal controls. J Alzheimers Dis. 2009;18(2):331-337.
  • Zhang T, Xiong H, Kan LX, et al. Genomic sequence, structural organization, molecular evolution, and aberrant rearrangement of promyelocytic leukemia zinc finger gene. Proc Natl Acad Sci U S A. 1999;96(20):11422- 11427.
  • Matsuzawa K, Izawa S, Ohkura T, et al. Implication of intracellular localization of transcriptional repressor PLZF in thyroid neoplasms. BMC Endocr Disord. 2014;14:52.
  • Chen X, Huang F, Qi Y, et al. Serum and thyroid tissue level of let-7b and their correlation with TRAb in Graves’ disease. J Transl Med. 2018;5;16(1):188.
  • Stefan M, Wei C, Lombardi A, et al. Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity. Proc Natl Acad Sci USA. 2014;111(34):12562-12567.
  • Rizzoti K, Lovell-Badge R. SOX3 activity during pharyngeal segmentation is required for craniofacial morphogenesis. Development. 2007;134(19):3437-3448.
  • Sun G, Fu L, Wen L, Shi YB. Activation of Sox3 gene by thyroid hormone in the developing adult intestinal stem cell during Xenopus metamorphosis. Endocrinology. 2014;155(12):5024-5032.
  • Huang J, Guo L. Knockdown of SOX9 inhibits the proliferation, invasion, and EMT in thyroid cancer cells. Oncol Res. 2017;25(2):167-176.
  • Endo T, Kobayashi T. Excess TSH causes abnormal skeletal development in young mice with hypothyroidism via suppressive effects on the growth plate. Am J Physiol Endocrinol Metab. 2013;305(5):E660-666.
  • Grimm D, Bauer J, Wise P, et al. The role of SOX family members in solid tumours and metastasis. Semin Cancer Biol. 2020;67(Pt 1):122-153.
  • Li JY, Han C, Zheng LL, Guo MZ. Epigenetic regulation of Wnt signaling pathway gene SRY-related HMG-box 17 in papillary thyroid carcinoma. Chin Med J (Engl). 2012;125(19):3526-3531.
  • Wang L, Shen YF, Shi ZM, Shang XJ, Jin DL, Xi F. Overexpression miR‐211‐5p hinders the proliferation, migration, and invasion of thyroid tumor cells by downregulating SOX 11. J Clin Lab Anal. 2018;32(3):e22293.
  • Horiguchi K, Nakakura T, Yoshida S, et al. Identification of THY1 as a novel thyrotrope marker and THY1 antibody-mediated thyrotrope isolation in the rat anterior pituitary gland. Biochem Biophys Res Commun. 2016;480(2):273-279.
  • Smith TJ, Sempowski GD, Berenson CS, Cao HJ, Wang HS, Phipps RP. Human thyroid fibroblasts exhibit a distinctive phenotype in culture: Characteristic ganglioside profile and functional CD40 expression. Endocrinology. 1997;138(12):5576-5588.
  • Saalbach A, Wetzig T, Haustein UF, Anderegg U. Detection of human soluble Thy-1 in serum by ELISA. Fibroblasts and activated endothelial cells are a possible source of soluble Thy-1 in serum. Cell Tissue Res. 1999;298(2):307-315.
There are 37 citations in total.

Details

Primary Language English
Subjects Health Services and Systems (Other)
Journal Section Özgün Araştırma
Authors

Hatice Nur Şeflek 0000-0003-2969-2322

Elif Gülbahçe Mutlu 0000-0003-2391-2152

Gökhan Cüce 0000-0003-1781-5292

Sabiha Serpil Kalkan 0000-0003-0076-9154

Publication Date August 20, 2024
Submission Date November 14, 2023
Acceptance Date March 8, 2024
Published in Issue Year 2024

Cite

APA Şeflek, H. N., Gülbahçe Mutlu, E., Cüce, G., Kalkan, S. S. (2024). THE EFFECT OF COENZYME Q10 ADMINISTRATION ON THE EXPRESSION OF Gdnf, Plzf, Sox3, Thy1 GENES IN RATS WITH HYPOTHYROIDISM. The Journal of Kırıkkale University Faculty of Medicine, 26(2), 129-135. https://doi.org/10.24938/kutfd.1390539
AMA Şeflek HN, Gülbahçe Mutlu E, Cüce G, Kalkan SS. THE EFFECT OF COENZYME Q10 ADMINISTRATION ON THE EXPRESSION OF Gdnf, Plzf, Sox3, Thy1 GENES IN RATS WITH HYPOTHYROIDISM. Kırıkkale Üni Tıp Derg. August 2024;26(2):129-135. doi:10.24938/kutfd.1390539
Chicago Şeflek, Hatice Nur, Elif Gülbahçe Mutlu, Gökhan Cüce, and Sabiha Serpil Kalkan. “THE EFFECT OF COENZYME Q10 ADMINISTRATION ON THE EXPRESSION OF Gdnf, Plzf, Sox3, Thy1 GENES IN RATS WITH HYPOTHYROIDISM”. The Journal of Kırıkkale University Faculty of Medicine 26, no. 2 (August 2024): 129-35. https://doi.org/10.24938/kutfd.1390539.
EndNote Şeflek HN, Gülbahçe Mutlu E, Cüce G, Kalkan SS (August 1, 2024) THE EFFECT OF COENZYME Q10 ADMINISTRATION ON THE EXPRESSION OF Gdnf, Plzf, Sox3, Thy1 GENES IN RATS WITH HYPOTHYROIDISM. The Journal of Kırıkkale University Faculty of Medicine 26 2 129–135.
IEEE H. N. Şeflek, E. Gülbahçe Mutlu, G. Cüce, and S. S. Kalkan, “THE EFFECT OF COENZYME Q10 ADMINISTRATION ON THE EXPRESSION OF Gdnf, Plzf, Sox3, Thy1 GENES IN RATS WITH HYPOTHYROIDISM”, Kırıkkale Üni Tıp Derg, vol. 26, no. 2, pp. 129–135, 2024, doi: 10.24938/kutfd.1390539.
ISNAD Şeflek, Hatice Nur et al. “THE EFFECT OF COENZYME Q10 ADMINISTRATION ON THE EXPRESSION OF Gdnf, Plzf, Sox3, Thy1 GENES IN RATS WITH HYPOTHYROIDISM”. The Journal of Kırıkkale University Faculty of Medicine 26/2 (August 2024), 129-135. https://doi.org/10.24938/kutfd.1390539.
JAMA Şeflek HN, Gülbahçe Mutlu E, Cüce G, Kalkan SS. THE EFFECT OF COENZYME Q10 ADMINISTRATION ON THE EXPRESSION OF Gdnf, Plzf, Sox3, Thy1 GENES IN RATS WITH HYPOTHYROIDISM. Kırıkkale Üni Tıp Derg. 2024;26:129–135.
MLA Şeflek, Hatice Nur et al. “THE EFFECT OF COENZYME Q10 ADMINISTRATION ON THE EXPRESSION OF Gdnf, Plzf, Sox3, Thy1 GENES IN RATS WITH HYPOTHYROIDISM”. The Journal of Kırıkkale University Faculty of Medicine, vol. 26, no. 2, 2024, pp. 129-35, doi:10.24938/kutfd.1390539.
Vancouver Şeflek HN, Gülbahçe Mutlu E, Cüce G, Kalkan SS. THE EFFECT OF COENZYME Q10 ADMINISTRATION ON THE EXPRESSION OF Gdnf, Plzf, Sox3, Thy1 GENES IN RATS WITH HYPOTHYROIDISM. Kırıkkale Üni Tıp Derg. 2024;26(2):129-35.

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