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TIP Revista Especializada en Ciencias Químico-Biológicas

2023, Número 1

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TIP Rev Esp Cienc Quim Biol 2023; 26 (1)


El tratamiento con testosterona regula positivamente los niveles de proteína y ARNm de la enzima superóxido dismutasa dependiente de Mn en los islotes pancreáticos de ratas macho (Rattus norvegicus)

Sosa-Larios TC, Morales-Miranda A, Palomar-Morales M, Rojas-Ochoa A, Rodríguez-Peña N, Morimoto S

Idioma: Español
Referencias bibliográficas: 45
Paginas: 1-11
Archivo PDF: 470.60 Kb.


RESUMEN

El aumento de la producción de especies reactivas de oxígeno daña a los islotes pancreáticos por estrés oxidativo y apoptosis en algunos modelos de diabetes en roedores. Se ha observado que la testosterona los protege contra este daño, sin embargo, no se conoce el mecanismo por el cual esta hormona ejerce su protección. El objetivo de este estudio fue evaluar el efecto de la administración de testosterona a ratas macho gonadectomizadas sobre la expresión de las enzimas antioxidantes, superóxido dismutasa dependiente de Mn (MnSOD) y catalasa. La expresión de las enzimas a nivel de la proteína, se estudió por inmunohistoquímica en ratas macho intactas, gonadectomizadas y gonadectomizadas tratadas con testosterona. La expresión del ARNm se analizó por retrotranscripción y reacción en cadena de la polimerasa en tiempo real, en islotes pancreáticos cultivados con testosterona, dihidrotestosterona (DHT) o vehículo. En el caso de la catalasa, el tratamiento con testosterona solamente aumentó la expresión del ARNm. La testosterona indujo la sobreexpresión de la proteína de MnSOD y del ARNm en los islotes pancreáticos a través de un mecanismo no relacionado con la aromatización androgénica, en el que muy probablemente intervienen los receptores de andrógenos, lo que demuestra la participación de la testosterona en la prevención de los daños causados por el estrés oxidativo en las células productoras de insulina.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Ahlbom, E., Prins, G. S. & Ceccatelli, S. (2001). Testosteroneprotects cerebellar granule cells from oxidative stressinducedcell death through a receptor mediated mechanism.Brain Research, 892(2), 255–262. https://doi.org/10.1016/s0006-8993(00)03155-3

  2. Alonso-Alvarez, C., Bertrand, S., Faivre, B., Chastel, O. &Sorci, G. (2007). Testosterone and oxidative stress: theoxidation handicap hypothesis. Proceedings. BiologicalSciences, 274(1611), 819–825. https://doi.org/10.1098/rspb.2006.3764

  3. Alonso-Magdalena, P., Morimoto, S., Ripoll, C., Fuentes, E.& Nadal, A. (2006). The estrogenic effect of bisphenol Adisrupts pancreatic beta-cell function in vivo and inducesinsulin resistance. Environmental Health Perspectives,114(1), 106–112. https://doi.org/10.1289/ehp.8451

  4. Beato, M. & Klug, J. (2000). Steroid hormone receptors: anupdate. Human Reproduction Update, 6(3), 225–236.https://doi.org/10.1093/humupd/6.3.225

  5. Díaz-Sánchez, V., Morimoto, S., Morales, A., Robles-Díaz, G. &Cerbón, M. (1995). Androgen receptor in the rat pancreas:genetic expression and steroid regulation. Pancreas, 11(3),241–245. https://doi.org/10.1097/00006676-199510000-00005

  6. Domingueti, C. P., Dusse, L. M., Carvalho, M.d, de Sousa, L. P.,Gomes, K. B. & Fernandes, A. P. (2016). Diabetes mellitus:The linkage between oxidative stress, inflammation,hypercoagulability and vascular complications. Journal ofDiabetes and its Complications, 30(4), 738–745. https://doi.org/10.1016/j.jdiacomp.2015.12.018

  7. Drews, G. & Düfer, M. (2012). Role of K(ATP) channels inβ-cell resistance to oxidative stress. Diabetes, Obesity &Metabolism, 14 Suppl 3, 120–128. https://doi.org/10.1111/j.1463-1326.2012.01644.x

  8. Eguchi, N., Vaziri, N. D., Dafoe, D. C. & Ichii, H. (2021). TheRole of Oxidative Stress in Pancreatic β Cell Dysfunctionin Diabetes. International Journal of Molecular Sciences,22(4), 1509. https://doi.org/10.3390/ijms22041509

  9. Guzmán, D. C., Mejía, G. B., Vázquez, I. E., García, E.H., del Angel, D. S. & Olguín, H. J. (2005). Effect oftestosterone and steroids homologues on indolaminesand lipid peroxidation in rat brain. The Journal of SteroidBiochemistry and Molecular Biology, 94(4), 369–373.https://doi.org/10.1016/j.jsbmb.2004.11.006

  10. Hammond, J., Le, Q., Goodyer, C., Gelfand, M., Trifiro, M. &LeBlanc, A. (2001). Testosterone-mediated neuroprotectionthrough the androgen receptor in human primary neurons.Journal of Neurochemistry, 77(5), 1319–1326. https://doi.org/10.1046/j.1471-4159.2001.00345.x

  11. Hanchang, W., Semprasert, N., Limjindaporn, T., Yenchitsomanus,P. T. & Kooptiwut, S. (2013). Testosterone protects againstglucotoxicity-induced apoptosis of pancreatic β-cells(INS-1) and male mouse pancreatic islets. Endocrinology,154(11), 4058–4067. https://doi.org/10.1210/en.2013-1351

  12. Harada, N., Katsuki, T., Takahashi, Y., Masuda, T., Yoshinaga,M., Adachi, T., Izawa, T., Kuwamura, M., Nakano, Y.,Yamaji, R. & Inui, H. (2015). Androgen receptor silencesthioredoxin-interacting protein and competitively inhibitsglucocorticoid receptor-mediated apoptosis in pancreaticβ-Cells. Journal of Cellular Biochemistry, 116(6), 998–1006. https://doi.org/10.1002/jcb.25054

  13. Harada, N., Yoda, Y., Yotsumoto, Y., Masuda, T., Takahashi,Y., Katsuki, T., Kai, K., Shiraki, N., Inui, H. & Yamaji,R. (2018). Androgen signaling expands β-cell mass inmale rats and β-cell androgen receptor is degraded underhigh-glucose conditions. American journal of physiology.Endocrinology and Metabolism, 314(3), E274–E286.https://doi.org/10.1152/ajpendo.00211.2017

  14. Kapoor, D., Goodwin, E., Channer, K. S. & Jones, T. H.(2006). Testosterone replacement therapy improvesinsulin resistance, glycaemic control, visceral adiposityand hypercholesterolaemia in hypogonadal men with type2 diabetes. European Journal of Endocrinology, 154(6),899–906. https://doi-org.pbidi.unam.mx:2443/10.1530/eje.1.02166

  15. King A. J. (2012). The use of animal models in diabetes research.British Journal ofPharmacology, 166(3), 877–894. https://doi.org/10.1111/j.1476-5381.2012.01911.x

  16. Kłapcińska, B., Jagsz, S., Sadowska-Krepa, E., Górski, J.,Kempa, K. & Langfort, J. (2008). Effects of castrationand testosterone replacement on the antioxidant defensesystem in rat left ventricle. The Journal of PhysiologicalSciences: JPS, 58(3), 173–177. https://doi.org/10.2170/physiolsci.RP002208

  17. Koukoulis, G. N., Filiponi, M., Gougoura, S., Befani, C.,Liakos, P. & Bargiota, Α. (2022). Testosterone anddihydrotestosterone modulate the redox homeostasis ofendothelium. Cell Biology International, 46(4), 660–670.https://doi.org/10.1002/cbin.11768

  18. Lee, Y. E., Kim, J. W., Lee, E. M., Ahn, Y. B., Song, K. H.,Yoon, K. H., Kim, H. W., Park, C. W., Li, G., Liu, Z. &Ko, S. H. (2012). Chronic resveratrol treatment protectspancreatic islets against oxidative stress in db/db mice.PLOS ONE, 7(11), e50412. https://doi.org/10.1371/journal.pone.0050412

  19. Lenzen S. (2017). Chemistry and biology of reactive specieswith special reference to the antioxidative defence status inpancreatic β-cells. Biochimica et Biophysica Acta. GeneralSubjects, 1861(8), 1929–1942. https://doi.org/10.1016/j.bbagen.2017.05.013

  20. Le May, C., Chu, K., Hu, M., Ortega, C. S., Simpson, E. R.,Korach, K. S., Tsai, M. J. & Mauvais-Jarvis, F. (2006).Estrogens protect pancreatic beta-cells from apoptosisand prevent insulin-deficient diabetes mellitus in mice.Proceedings of the National Academy of Sciences of theUnited States of America, 103(24), 9232–9237. https://doi.org/10.1073/pnas.0602956103

  21. Li, R. J., Qiu, S. D., Wang, H. X., Tian, H., Wang, L. R. & Huo,Y. W. (2008). Androgen receptor: a new player associatedwith apoptosis and proliferation of pancreatic beta-cell intype 1 diabetes mellitus. Apoptosis: an International Journalon Programmed Cell Death, 13(8), 959–971. https://doi.org/10.1007/s10495-008-0230-9

  22. Lin, B., Wang, J., Hong, X., Yan, X., Hwang, D., Cho, J. H.,Yi, D., Utleg, A. G., Fang, X., Schones, D. E., Zhao, K.,Omenn, G. S. & Hood, L. (2009). Integrated expressionprofiling and ChIP-seq analyses of the growth inhibitionresponse program of the androgen receptor. PLOS ONE,4(8), e6589. https://doi.org/10.1371/journal.pone.0006589

  23. Meydan, S., Kus, I., Tas, U., Ogeturk, M., Sancakdar, E.,Dabak, D. O., Zararsız, I. & Sarsılmaz, M. (2010).Effects of testosterone on orchiectomy-induced oxidativedamage in the rat hippocampus. Journal of ChemicalNeuroanatomy, 40(4), 281–285. https://doi.org/10.1016/j.jchemneu.2010.07.006

  24. Mizukami, H., Takahashi, K., Inaba, W., Tsuboi, K., Osonoi,S., Yoshida, T. & Yagihashi, S. (2014). Involvement ofoxidative stress-induced DNA damage, endoplasmicreticulum stress, and autophagy deficits in the decline ofβ-cell mass in Japanese type 2 diabetic patients. DiabetesCare, 37(7), 1966–1974. https://doi.org/10.2337/dc13-2018

  25. Morimoto, S., Fernandez-Mejia, C., Romero-Navarro,G., Morales-Peza, N. & Díaz-Sánchez, V. (2001).Testosterone effect on insulin content, messengerribonucleic acid levels, promoter activity, and secretionin the rat. Endocrinology, 142(4), 1442–1447. https://doi.org/10.1210/endo.142.4.8069

  26. Morimoto, S., Mendoza-Rodríguez, C. A., Hiriart, M., Larrieta,M. E., Vital, P. & Cerbón, M. A. (2005). Protective effectof testosterone on early apoptotic damage induced bystreptozotocin in rat pancreas. The Journal of Endocrinology,187(2), 217–224. https://doi.org/10.1677/joe.1.06357

  27. Navarro, G., Allard, C., Morford, J. J., Xu, W., Liu, S., Molinas,A. J., Butcher, S. M., Fine, N. H., Blandino-Rosano, M.,Sure, V. N., Yu, S., Zhang, R., Münzberg, H., Jacobson,D. A., Katakam, P. V., Hodson, D. J., Bernal-Mizrachi, E.,Zsombok, A. & Mauvais-Jarvis, F. (2018). Androgen excessin pancreatic β cells and neurons predisposes female miceto type 2 diabetes. JCI Insight, 3(12), e98607. https://doi.org/10.1172/jci.insight.98607

  28. Paik, S. G., Michelis, M. A., Kim, Y. T. & Shin, S. (1982).Induction of insulin-dependent diabetes by streptozotocin.Inhibition by estrogens and potentiation by androgens.Diabetes, 31(8 Pt 1), 724–729. https://doi.org/10.2337/diab.31.8.724

  29. Palomar-Morales, M., Morimoto, S., Mendoza-Rodríguez,C. A. & Cerbón, M. A. (2010). The protective effect oftestosterone on streptozotocin-induced apoptosis in betacells is sex specific. Pancreas, 39(2), 193–200. https://doi.org/10.1097/MPA.0b013e3181c156d9

  30. Pang, S. T., Dillner, K., Wu, X., Pousette, A., Norstedt, G.& Flores-Morales, A. (2002). Gene expression profilingof androgen deficiency predicts a pathway of prostateapoptosis that involves genes related to oxidativestress. Endocrinology, 143(12), 4897–4906. https://doi.org/10.1210/en.2002-220327

  31. Parasuraman, S., Raveendran, R. & Kesavan, R. (2010). Bloodsample collection in small laboratory animals. Journal ofPharmacology & Pharmacotherapeutics, 1(2), 87–93.https://doi.org/10.4103/0976-500X.72350

  32. Pousette A. (1976). Demonstration of an androgen receptor inrat pancreas. The Biochemical Journal, 157(1), 229–232.https://doi.org/10.1042/bj1570229

  33. Rao, P. M., Kelly, D. M. & Jones, T. H. (2013). Testosterone andinsulin resistance in the metabolic syndrome and T2DMin men. Nature Reviews. Endocrinology, 9(8), 479–493.https://doi.org/10.1038/nrendo.2013.122

  34. Ritschl, L. M., Fichter, A. M., Häberle, S., von Bomhard, A.,Mitchell, D. A., Wolff, K. D. & Mücke, T. (2015). Ketamine-Xylazine Anesthesia in Rats: Intraperitoneal versusIntravenous Administration Using a Microsurgical FemoralVein Access. Journal of Reconstructive Microsurgery,31(5), 343–347. https://doi.org/10.1055/s-0035-1546291

  35. Sadowska-Krępa, E., Kłapcińska, B., Jagsz, S., Nowara, A.,Szołtysek-Bołdys, I., Chalimoniuk, M., Langfort, J. &Chrapusta, S. J. (2017). High-dose testosterone enanthatesupplementation boosts oxidative stress, but exerts littleeffect on the antioxidant barrier in sedentary adolescent malerat liver. Pharmacological Reports: PR, 69(4), 673–678.https://doi.org/10.1016/j.pharep.2017.02.023

  36. Salazar-García, M. & Corona, J. C. (2021). The use of naturalcompounds as a strategy to counteract oxidative stress inanimal models of diabetes mellitus. International Journal ofMolecular Sciences, 22(13), 7009. https://doi.org/10.3390/ijms22137009

  37. Sasikumar, R., Jyoti Das, A. & Chandra Deka, S. (2021). Invitro cytoprotective activity of cyanidin 3-glucoside extractsfrom Haematocarpus validus pomace on streptozotocininduced oxidative damage in pancreatic β-cells. SaudiJournal of Biological Sciences, 28(9), 5338–5348. https://doi.org/10.1016/j.sjbs.2021.05.065

  38. Sies, H. & Jones, D. P. (2020). Reactive oxygen species (ROS)as pleiotropic physiological signalling agents. Naturereviews. Molecular Cell Biology, 21(7), 363–383. https://doi.org/10.1038/s41580-020-0230-3

  39. Son, S. W., Lee, J. S., Kim, H. G., Kim, D. W., Ahn, Y. C. &Son, C. G. (2016). Testosterone depletion increases thesusceptibility of brain tissue to oxidative damage in arestraint stress mouse model. Journal of Neurochemistry,136(1), 106–117. https://doi.org/10.1111/jnc.13371

  40. Wang, N., Yi, W. J., Tan, L., Zhang, J. H., Xu, J., Chen, Y.,Qin, M., Yu, S., Guan, J. & Zhang, R. (2017). Apigeninattenuates streptozotocin-induced pancreatic β cell damageby its protective effects on cellular antioxidant defense. Invitro Cellular & Developmental Biology. Animal, 53(6),554–563. https://doi.org/10.1007/s11626-017-0135-4

  41. Xu, W., Niu, T., Xu, B., Navarro, G., Schipma, M. J. &Mauvais-Jarvis, F. (2017). Androgen receptor-deficientislet β-cells exhibit alteration in genetic markers ofinsulin secretion and inflammation. A transcriptomeanalysis in the male mouse. Journal of Diabetes and itsComplications, 31(5), 787–795. https://doi.org/10.1016/j.jdiacomp.2017.03.002

  42. Yao, Q. M., Wang, B., An, X. F., Zhang, J. A. & Ding, L.(2018). Testosterone level and risk of type 2 diabetes inmen: a systematic review and meta-analysis. EndocrineConnections, 7(1), 220–231. https://doi.org/10.1530/EC-17-0253

  43. Yaribeygi, H., Sathyapalan, T., Atkin, S. L. & Sahebkar,A. (2020). Molecular Mechanisms Linking OxidativeStress and Diabetes Mellitus. Oxidative Medicineand Cellular Longevity, 2020, 8609213. https://doi.org/10.1155/2020/8609213

  44. Zhang, Y., Mei, H., Shan, W., Shi, L., Chang, X., Zhu, Y.,Chen, F. & Han, X. (2016). Lentinan protects pancreaticβ cells from STZ-induced damage. Journal of Cellularand Molecular Medicine, 20(10), 1803–1812. https://doi.org/10.1111/jcmm.12865

  45. Zatroch, K. K., Knight, C. G., Reimer, J. N. & Pang, D. S.(2017). Refinement of intraperitoneal injection of sodiumpentobarbital for euthanasia in laboratory rats (Rattusnorvegicus). BMC Veterinary Research, 13(1), 60. https://doi.org/10.1186/s12917-017-0982-y




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