Genç ve Yaşlı Ratların Kalp Dokularında Klotho, Endotelial Nitrit Oksit Sentetaz ve Katalaz Genlerinin İfade Düzeyleri

Amaç: Bu çalışmada rat kalp dokularında yaşlanma metabolizmasında önemli olduğu düşünülen Klotho (KL), Endotelial nitrik oksit sentaz (e-NOS), Katalaz (CAT) genlerinin, yaşlanma ile ortaya çıkabilecek gen ifade düzeyleri ve meydana gelen değişiklikler incelenmiştir. Gereç ve Yöntem: Bu genlerin ifade düzeyleri 24 aylık ve 6 aylık erkek Wistar ratların kalp dokularında eş zamanlı polimeraz zincir reaksiyonu yöntemi kullanılarak karşılaştırılmıştır. Bulgular: Elde edilen sonuçlar değerlendirildiğinde, e-NOS mRNA düzeyi yaşlı ratların sol kalp bölgesinde belirgin olarak yüksek bulunmuş, aynı grubun kalplerinin sağ kısmında da yüksek olmasına rağmen istatistiksel olarak anlamlı olmadığı görülmüştür. CAT geni, mRNA düzeyi yaşlı rat kalp dokularının sadece sol kısmında genç ratlara göre anlamlı olarak düşük bulunmuştur. Diğer taraftan, yaşlı ratların sağ kalp kısmındaki dokuda ölçülen katalaz mRNA düzeyi, genç ratların aynı bölgesinden elde edilen dokudaki katalaz mRNA düzeyi ile karşılaştırıldığında daha yüksek bulunmuştur. Ancak, KL geninin ifadesi gerek genç ve gerekse yaşlı ratların kalp dokularının sol kısmında anlamlı olarak farklılık göstermemiş olup, aynı grubun sağ bölgesinde ise yaşlı ratlarda genç ratlara göre, gen ifade düzeyinin anlamlı olarak arttığı saptanmıştır. Sonuç: Yaşlanma olgusunda, KL, e-NOS ve CAT genlerinin rat kalp dokusunda etkin olabileceği düşünülmektedir. Bu alanda yapılacak daha detaylı çalışmaların, yaşlanma ile görünme riski artan kardiyovasküler hastalıkların tanı ve tedavisinde önemli rol oynayabileceği düşünülmektedir.

The Expression Levels of Klotho, Endothelial Nitrite Oxide Synthetase and Catalase Genes of the Heart Tissues of Young and Old Rats

Objectives: In order to evaluate the role of genes in aging process in the heart of rats, the expression levels of Klotho (KL), Endothelial nitrite oxidesynthase (e-NOS) and Catalase (CAT) genes, which are thought to be important in the metabolism, were investigated in the present study.Materials and Methods: The expression levels of these genes were compared in heart tissues of 24-month-old and 6-month-old male Wistar ratsusing real time polymerase chain reaction method.Results: The mRNA level of e-NOS gene was increased significantly in the left side of the hearts of old rats, it was also increased in the right sideof the heart, but it was not statistically significant. The mRNA level of CAT gene was decreased significantly in only the left side of the old rat heartcompared to that of the young rat. Furthermore, our data on mRNA level of CAT gene determined in the right part of the heart were increased inthat of old rats compared to those of the young rats. However, the expression level of KL gene was not significantly different in the left part of thehearts in either old rats or young rats, whereas the expression level of this gene was increased significantly in the right side of the old rat heartcompared to that of young rat heart.Conclusion: KL, e-NOS and CAT expressions were thought to be effective in the heart tissue of rats in aging process. Further detailed studies thatshould be designed on this subject could play important role in the diagnosis and treatment of cardiovascular diseases in which the occurrence riskis increased by the aging process.

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1. Lopez-Otin C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell. 2013;153:1194-1217.
2. Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997;390:45-51.
3. Poelzl G, Ghadge SK, Messner M, et al. Klotho is upregulated in human cardiomyopathy independently of circulating Klotho levels. Sci Rep. doi: 10.1038/s41598-018-26539-6
4. Ji N, Luan J, Hu F, et al. Aerobic exercise-stimulated Klotho upregulation extends life span by attenuating the excess production of reactive oxygen species in the brain and kidney. Exp Ther Med. 2018;16:3511-3517.
5. Wang Y, Sun Z. Current understanding of klotho. Ageing Res Rev. 2009;8:43- 51.
6. Wang X, Hu S, Liu L. Phosphorylation and acetylation modifications of FOXO3a: Independently or synergistically? Oncol Lett. 2017;13:2867-2872.
7. Pathare G, Vk S, Shalia K. Emerging Roles of Klotho in Cardiovascular Diseases. JCCR. doi: 10.15406/jccr.2016.06.00228
8. Saito Y, Yamagishi T, Nakamura T, et al. Klotho protein protects against endothelial dysfunction. Biochem Biophys Res Commun. 1998;248:324-329.
9. Olgar Y, Turan B. A sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin comparison with insulin shows important effects on Zn(2+)- transporters in cardiomyocytes from insulin-resistant metabolic syndrome rats through inhibition of oxidative stress (1). Can J Physiol Pharmacol. 2019;97:528-535.
10. Georgiou A, Lisacek-Kiosoglous A, Yiallouris A, et al. Klotho: The Protein of Faith. Ecronicon. 2017:189-223.
11. Mitani H, Ishizaka N, Aizawa T, et al. In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage. Hypertension. 2002;39:838-843.
12. Jimbo R, Kawakami-Mori F, Mu S, et al. Fibroblast growth factor 23 accelerates phosphate-induced vascular calcification in the absence of Klotho deficiency. Kidney Int. 2014;85:1103-1111.
13. Aizawa H, Saito Y, Nakamura T, et al. Downregulation of the Klotho gene in the kidney under sustained circulatory stress in rats. Biochem Biophys Res Commun. 1998;249:865-871.
14. Xie J, Cha SK, An SW, et al. Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart. Nat Commun. doi: 10.1038/ncomms2240
15. Hu MC, Kuro-o M, Moe OW. Klotho and chronic kidney disease. Contrib Nephrol. 2013;180:47-63.
16. Alhusseini NF, AEDA El-Talees, Hussien NI, Arafat NN. The Effects of Exercise and Antioxidant on Klotho Gene Expression During Oxidative Stress in Rat’s Cardiac Tissue. SDRP Journal of Cellular and Molecular Physiology. 2016;1:15-24.
17. Ai F, Chen M, Li W, et al. Protective role of Klotho on cardiomyocytes upon hypoxia/reoxygenation via downregulation of Akt and FOXO1 phosphorylation. Mol Med Rep. 2014;11:2013-2019.
18. Aguilar-Alonso P, Vera-Lopez O, Brambila-Colombres E, et al. Evaluation of Oxidative Stress in Cardiomyocytes during the Aging Process in Rats Treated with Resveratrol. Oxid Med Cell Longev. 2018;2018:1-9.
19. Dehghani A, Hafizibarjin Z, Najjari R, et al. Resveratrol and 1,25-dihydroxyvitamin D co-administration protects the heart against D-galactose-induced aging in rats: evaluation of serum and cardiac levels of klotho. Aging Clin Exp Res. 2018;31:1195-1205.
20. Torella D, Leosco D, Indolfi C, et al. Aging exacerbates negative remodeling and impairs endothelial regeneration after balloon injury. Am J Physiol Heart Circ Physiol. 2004;287:H2850-H2860.
21. Griecsova L, Farkasova V, Gablovsky I, et al. Effect of maturation on the resistance of rat hearts against ischemia. Study of potential molecular mechanisms. Physiol Res. 2015:S685-S696.