Publicado

2024-01-22

THE DOSE-DEPENDENT EFFECTS OF CAFFEINE AND BETAINE ON TELOMERASE ENZYME ACTIVITY IN MICE

Los efectos dependientes de la dosis de cafeína y betaína sobre la actividad de la enzima telomerasa en ratones

DOI:

https://doi.org/10.15446/abc.v29n2.99155

Palabras clave:

Betaine, Caffeine, Catalase, SOD, Telomerase (en)
Betaína, Cafeína, Catalasa, SOD, Telomerasa (es)

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Autores/as

The telomerase enzyme, which extends the Deoxyribonucleic Acid (DNA) regions called telomeres at the ends of the chromosomes, has an important place in aging, cancer and stem cell studies. In this study, the effects of betaine and caffeine on telomerase enzyme activity in mice were investigated. Telomerase activity was measured by a Polymerase Chain Reaction-Enzyme Linked Immunosorbent Assay (PCR-ELISA) based method. The activity of Superoxide Dismutase (SOD) and Catalase enzymes in the liver and kidney and the amount of Malondialdehyde (MDA) were also investigated. The results show that betaine has a slightly inhibitory effect (not significant) on telomerase activity, especially at high doses. Caffeine may act as an inhibitor in high doses but may have an activator effect at low doses. Also, it was observed that SOD and Catalase enzyme activities were parallel to the increase/decrease in telomerase enzyme activity in the liver.

La enzima telomerasa, que extiende las regiones del ácido desoxirribonucleico (ADN) llamadas telómeros en los extremos de los cromosomas, ocupa un lugar importante en los estudios sobre el envejecimiento, el cáncer y las células madre. En este estudio, se investigaron los efectos de la betaína y la cafeína sobre la actividad de la enzima telomerasa en ratones. La actividad de la telomerasa se midió mediante un método basado en PCR-ELISA. También se investigó la actividad de las enzimas SOD y catalasa en hígado y riñón y la cantidad de MDA. Los resultados muestran que la betaína tiene un efecto levemente inhibidor (no significativo) sobre la actividad de la telomerasa, especialmente a dosis altas. La cafeína puede actuar como inhibidor en dosis altas, pero puede tener un efecto activador en dosis bajas. Se observó que las actividades de la enzima SOD y catalasa eran paralelas al aumento / disminución de la actividad de la enzima telomerasa en el hígado.

Referencias

Arnaud MJ. 1999. Caffeine: chemistry and physiological effects. Encyclopedia of Hum. Nutr. 1: 206-214.

Artandi SE, DePinho RA. 2010. Telomeres and telomerase in cancer. Carcinog. 31(1): 9-18. doi: https://doi.org/10.1093/carcin/bgp268

Blasco MA. 2005. Telomeres and human disease: ageing, cancer and beyond. Nat. Rev. Genet. 6(8): 611-622. doi: https://doi.org/10.1038/nrg1656

Blasco MA. 2007. The epigenetic regulation of mammalian telomeres. Nat. Rev. Genet. 8(4): 299-309. doi: https://doi.org/10.1038/nrg2047

Boccardi V, Paolisso G. 2014. Telomerase activation: a potential key modulator for human healthspan and longevity. Ageing Res. Rev. 15:1-5. doi: https://doi.org/10.1016/j.arr.2013.12.006.

Buseman CM, Wright WE, Shay JW. 2012. Is telomerase a viable target in cancer? Mutat. Res-Fund. Mol. M. 730(1-2):90-97. doi: https://doi.org/10.1016/j.mrfmmm.2011.07.006.

Chen J, Zhou X, Wu W, Wang X, Wang Y. 2015. FTOdependent function of N6-methyladenosine is involved in the hepatoprotective effects of betaine on adolescent mice. J. Physiol. Biochem. 71(3):405-413. doi: https://doi.org/10.1007/s13105-015-04201

Cooney CA. 1993. Are somatic cells inherently deficient in methylation metabolism? A proposed mechanism for DNA methylation loss, senescence and aging. Growth Dev. Aging. 57(4): 261-273.

Day CR, Kempson SA. 2016. Betaine chemistry, roles, and potential use in liver disease. Biochim. Biophys. Acta–Gen. Subj. 1860(6):1098-1106. doi: https://doi.org/10.1016/j.bbagen.2016.02.001

De Jesus BB, Blasco MA. 2013. Telomerase at the intersection of cancer and aging. Trends Genet. 29(9): 513-520. doi: https://doi.org/10.1016/j.tig.2013.06.007

De Jesus BB, Vera E, Schneeberger K, Tejera AM, Ayuso E, Bosch F, Blasco MA. 2012. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol. Med. 4(8):691-704. doi: https://doi.org/10.1002/emmm.201200245

Garrett Q, Khandekar N, Shih S, Flanagan JL, Simmons P, Vehige J, Willcox MDP. 2013. Betaine stabilizes cell volume and protects against apoptosis in human corneal epithelial cells under hyperosmotic stress. Exp. Eye Res. 108:33-41. doi: https://doi.org/10.1016/j.exer.2012.12.001

Graf D, Kurz AK, Reinehr R, Fischer R, Kircheis G, Häussinger D. 2002. Prevention of bile acid–induced apoptosis by betaine in rat liver. Hepatol. 36(4):829-839. doi: https://doi.org/10.1053/jhep.2002.35536

Granger MP, Wright WE, Shay JW. 2002. Telomerase in cancer and aging. Crit. Rev. Oncol. Hematol. 41(1): 29–40. doi: https://doi.org/10.1016/S1040-8428(01)00188-3.

Hagar H, Husain S, Fadda LM, Attia NM, Attia MM, Ali HM. 2019. Inhibition of NF-κB and the oxidative stressdependent caspase-3 apoptotic pathway by betaine supplementation attenuates hepatic injury mediated by cisplatin in rats. Pharmacol. Rep. 71(6): 1025-1033. doi: https://doi.org/10.1016/j.pharep.2019.06.003

Hemann MT, Strong MA, Hao LY, Greider CW. 2001. The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell. 107(1):67-77. doi: https://doi.org/10.1016/S0092-8674(01)00504-9.

Hiyama E, Hiyama K. 2007. Telomere and telomerase in stem cells. Br. J. Cancer. 96:1020–1024. doi: https://doi.org/10.1038/sj.bjc.6603671

[IARC] International Agency for Research on Cancer. 1991. Caffeine IARC monographs on the evaluation of carcinogenic risks to humans. 51:291–390.

Ji C, Kaplowitz N. 2003. Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice. Gastroenterol. 124(5):1488-1499. doi: https://doi.org/10.1016/S0016-5085(03)00276-2

Jiang J, Wang Y, Sušac L, Chan H, Basu R, Zhou ZH, Feigon J. 2018. Structure of telomerase with telomeric DNA. Cell. 173(5):1179-1190. doi: https://doi.org/10.1016/j.cell.2018.04.038.

Jung YS, Kim SJ, Ahn CW, Kim YS, Choi DW, Kim YC. 2013. Alleviation of alcoholic liver injury by betaine involves an enhancement of antioxidant defense via regulation of sulfur amino acid metabolism. Food Chem. Toxicol. 62:292-298. doi: https://doi.org/10.1016/j.fct.2013.08.049

Khodayar MJ, Kalantari H, Khorsandi L, Rashno M, Zeidooni L. 2018. Betaine protects mice against acetaminophen hepatotoxicity possibly via mitochondrial complex II and glutathione availability. Biomed. Pharmacother. 103:1436-1445. doi: https://doi.org/10.1016/j.biopha.2018.04.154

Kim SK, Seo JM, Chae YR, Jung YS, Park JH, Kim YC. 2009. Alleviation of dimethylnitrosamine-induced liver injury and fibrosis by betaine supplementation in rats. Chem. Biol. Interact. 177(3):204-211. doi: https://doi.org/10.1016/j.cbi.2008.09.021.

KimW, Ludlow AT, Min J, Robin JD, Stadler G, Mender I, Lai T, Zhang N, Wright WE, Shay JW. 2016. Regulation of the human telomerase gene TERT by telomere position effect over long distances (TPE-OLD): implications for aging and cancer. PLoS Biol. 14(12):e2000016. doi: https://doi.org/10.1371/journal.pbio.2000016

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. Clin Interv Aging. 13:757. doi: http://dx.doi.org/10.2147/CIA.S158513.

Liu JJ, Crous-Bou M, Giovannucci E, De Vivo I. 2016. Coffee Consumption Is Positively Associated with Longer Leukocyte Telomere Length in the Nurses’ Health Study. J Nutr. 146(7):1373-1378. doi: https://doi.org/10.3945/jn.116.230490

Lowry OH, Rosebrough NJ, Faar AL, Randall RJ. 1951. Protein measurement with the folin phenol reagent. J. Biol. Chem. 193:265–275. doi: https://doi.org/10.1016/S0021-9258(19)52451-6

Luck H. 1963. Catalase. In H.U. Bergmeyer Eds. Methods of Enzymatic Analyses. Verlag Chemie Academic Press, Weinheim, New York. p. 885-894.

Mahmoudnia N, Madani Y. 2012. Effect of betaine on performance and carcass composition of broiler chicken in warm weather-a review. Int. J. Agric. Sci. 2(8): 675-683.

Mutlu AG. 2017. Telomerase Inhibitors and Activators: Pharmaceutical Importance. In M. Senturk Eds. Enzyme Inhibitors and Activators. InTech, Rijeka, Croatia. p. 125-138.

Nemmar A, Al-Salam S, Beegam S, Yuvaraju P, Oulhaj A, Ali BH. 2017. Water-pipe smoke exposure-induced circulatory disturbances in mice, and the influence of betaine supplementation thereon. Cell. Physiol. Biochem. doi: 41(3): 1098-1112. doi: https://doi.org/10.1159/000464117

Newberne PM, Rogers AE. 1986. Labile methyl groups and the promotion of cancer. Annu. Rev. Nutr. 6(1): 407-432. doi: https://doi.org/10.1146/annurev.nu.06.070186.002203

Olovnikov AM. 1996. Telomeres, telomerase, and aging: origin of the theory. Exp. Gerontol. 31(4): 443-448. doi: https://doi.org/10.1016/0531-5565(96)00005-8.

Preedy VR. 2015. Betaine: Chemistry, analysis, function and effects. R. Soc. Chem. doi: https://doi.org/10.1039/9781782628446

Prowse KR, Greider CW. 1995. Developmental and tissuespecific regulation of mouse telomerase and telomere length. Proc. Natl. Acad. Sci. 92(11):4818-4822. doi: https://doi.org/10.1073/pnas.92.11.4818

Ratriyanto A, Mosenthin R, Bauer E, Eklund M. 2009. Metabolic, osmoregulatory and nutritional functions of betaine in monogastric animals. Asian Australas. J. Anim. Sci. 22(10): 1461-1476. doi: https://doi.org/10.5713/ajas.2009.80659.

Reichert S, Stier A. 2017. Does oxidative stress shorten telomeres in vivo? A Review. Biol. Lett. 13(12): 20170463. doi: https://doi.org/10.1098/rsbl.2017.0463

Sanchis-Gomar F, Lucia A. 2015. Acute myocardial infarction: ‘telomerasing’ for cardioprotection. Trends Mol. Med. 21(4):203-205. doi:https://doi.org/10.1016/j.molmed.2015.02.001

Sandin S, Rhodes D. 2014. Telomerase structure. Curr. Opin. Struct. Biol. 25:104-110. doi: https://doi.org/10.1016/j.sbi.2014.02.003

Schwahn BC, Hafner D, Hohlfeld T, Balkenhol N, Laryea MD, Wendel U. 2003. Pharmacokinetics of oral betaine in healthy subjects and patients with homocystinuria. Br. J. Clin. Pharmacol. 55(1):6-13. doi: https://doi.org/10.1046/j.1365-2125.2003.01717.x

Shadmehr S, Tabatabaei SRF, Hosseinifar S, Tabandeh MR, Amiri A. 2018. Attenuation of heat stressinduced spermatogenesis complications by betaine in mice. Theriogenology. 106:117-126. doi: https://doi.org/10.1016/j.theriogenology.2017.10.008

Shay JW, Wright WE. 2001. Telomeres and telomerase: Implications for cancer and aging. Radiat Res. 155(1):188-193. doi: https://doi.org/10.1667/0033-7587(2001)155[0188:TATIFC]2.0.CO;2

Shay JW, Wright WE. 2002. Telomerase: A target for cancer therapeutics. Cancer Cell. 2(4): 257–262. doi: https://doi.org/10.1016/S1535-6108(02)00159-9

Sprouse AA, Steding CE, Herbert BS. 2012. Pharmaceutical regulation of telomerase and its clinical potential. J. Cell Mol Med. 16(1):1-7. doi:https://doi.org/10.1111/j.1582-4934.2011.01460.x

Tao L, Zhang W, Zhang Y, Zhang M, Zhang Y, Niu X, Zhao Q, Liu Z, Li Y, Diao A. 2021. Caffeine promotes the expression of telomerase reverse transcriptase to regulate cellular senescence and aging. Food Funct. 12(7):2914-2924. doi: https://doi.org/10.1039/D0FO03246H

Tárkányi I, Aradi J. 2008. Pharmacological intervention strategies for affecting telomerase activity: Future prospects to treat cancer and degenerative disease. Biochim. 90(1):156-172. doi: https://doi.org/10.1016/j.biochi.2007.09.002

Tsunoda K, Sato A, Kurata R, Mizuyama R, Shimegi S. 2019. Caffeine improves contrast sensitivity of freely moving rats. Physiol. Behav. 199:111-117. doi: https://doi.org/10.1016/j.physbeh.2018.11.014

Tucker LA. 2017. Caffeine consumption and telomere length in men and women of the National Health and Nutrition Examination Survey (NHANES). Nutr. Metab. 14(10). doi: https://doi.org/10.1186/s12986-017-0162-x

Ueland PM. 2011. Choline and betaine in health and disease. J. Inherit. Metab. Dis. 34(1):3-15. doi: https://doi.org/10.1007/s10545-010-9088-4

Wasowicz W, Neve J, Peretz A. 1993. Optimized steps in fluorometric determination of thiobarbituric acidreactive substances in serum: importance of extraction pH and influence of sample preservation and storage. Clin. Chem. 39(12): 2522-2526. doi: https://doi.org/10.1093/clinchem/39.12.2522

Xia L, Wang XX, Hu XS, Guo XG, Shang YP, Chen HJ, Zeng CL, Zhang FR., Chen JZ. 2008. Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms. Br. J. Pharmacol. 155(3):387-394. doi: https://doi.org/10.1038/bjp.2008.272

Zeisel SH, Mar MH, Howe JC, Holden JM. 2003. Concentrations of choline-containing compounds and betaine in common foods. J Nutr. 133(5):1302-1307. doi: https://doi.org/10.1093/jn/133.5.1302

Cómo citar

APA

Tikirdik, M., Mutlu, A. G., Alkan, I., Yildiz, H., Korkmaz, D. y Topal, A. (2023). THE DOSE-DEPENDENT EFFECTS OF CAFFEINE AND BETAINE ON TELOMERASE ENZYME ACTIVITY IN MICE. Acta Biológica Colombiana, 29(2), 5–11. https://doi.org/10.15446/abc.v29n2.99155

ACM

[1]
Tikirdik, M., Mutlu, A.G., Alkan, I., Yildiz, H., Korkmaz, D. y Topal, A. 2023. THE DOSE-DEPENDENT EFFECTS OF CAFFEINE AND BETAINE ON TELOMERASE ENZYME ACTIVITY IN MICE. Acta Biológica Colombiana. 29, 2 (dic. 2023), 5–11. DOI:https://doi.org/10.15446/abc.v29n2.99155.

ACS

(1)
Tikirdik, M.; Mutlu, A. G.; Alkan, I.; Yildiz, H.; Korkmaz, D.; Topal, A. THE DOSE-DEPENDENT EFFECTS OF CAFFEINE AND BETAINE ON TELOMERASE ENZYME ACTIVITY IN MICE. Acta biol. Colomb. 2023, 29, 5-11.

ABNT

TIKIRDIK, M.; MUTLU, A. G.; ALKAN, I.; YILDIZ, H.; KORKMAZ, D.; TOPAL, A. THE DOSE-DEPENDENT EFFECTS OF CAFFEINE AND BETAINE ON TELOMERASE ENZYME ACTIVITY IN MICE. Acta Biológica Colombiana, [S. l.], v. 29, n. 2, p. 5–11, 2023. DOI: 10.15446/abc.v29n2.99155. Disponível em: https://revistas.unal.edu.co/index.php/actabiol/article/view/99155. Acesso em: 17 jul. 2024.

Chicago

Tikirdik, Muazzez, Ayse Gul Mutlu, Irem Alkan, Hulya Yildiz, Didem Korkmaz, y Aykut Topal. 2023. «THE DOSE-DEPENDENT EFFECTS OF CAFFEINE AND BETAINE ON TELOMERASE ENZYME ACTIVITY IN MICE». Acta Biológica Colombiana 29 (2):5-11. https://doi.org/10.15446/abc.v29n2.99155.

Harvard

Tikirdik, M., Mutlu, A. G., Alkan, I., Yildiz, H., Korkmaz, D. y Topal, A. (2023) «THE DOSE-DEPENDENT EFFECTS OF CAFFEINE AND BETAINE ON TELOMERASE ENZYME ACTIVITY IN MICE», Acta Biológica Colombiana, 29(2), pp. 5–11. doi: 10.15446/abc.v29n2.99155.

IEEE

[1]
M. Tikirdik, A. G. Mutlu, I. Alkan, H. Yildiz, D. Korkmaz, y A. Topal, «THE DOSE-DEPENDENT EFFECTS OF CAFFEINE AND BETAINE ON TELOMERASE ENZYME ACTIVITY IN MICE», Acta biol. Colomb., vol. 29, n.º 2, pp. 5–11, dic. 2023.

MLA

Tikirdik, M., A. G. Mutlu, I. Alkan, H. Yildiz, D. Korkmaz, y A. Topal. «THE DOSE-DEPENDENT EFFECTS OF CAFFEINE AND BETAINE ON TELOMERASE ENZYME ACTIVITY IN MICE». Acta Biológica Colombiana, vol. 29, n.º 2, diciembre de 2023, pp. 5-11, doi:10.15446/abc.v29n2.99155.

Turabian

Tikirdik, Muazzez, Ayse Gul Mutlu, Irem Alkan, Hulya Yildiz, Didem Korkmaz, y Aykut Topal. «THE DOSE-DEPENDENT EFFECTS OF CAFFEINE AND BETAINE ON TELOMERASE ENZYME ACTIVITY IN MICE». Acta Biológica Colombiana 29, no. 2 (diciembre 27, 2023): 5–11. Accedido julio 17, 2024. https://revistas.unal.edu.co/index.php/actabiol/article/view/99155.

Vancouver

1.
Tikirdik M, Mutlu AG, Alkan I, Yildiz H, Korkmaz D, Topal A. THE DOSE-DEPENDENT EFFECTS OF CAFFEINE AND BETAINE ON TELOMERASE ENZYME ACTIVITY IN MICE. Acta biol. Colomb. [Internet]. 27 de diciembre de 2023 [citado 17 de julio de 2024];29(2):5-11. Disponible en: https://revistas.unal.edu.co/index.php/actabiol/article/view/99155

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