EFFECT OF CHRONIC STRESS ON SERUM AND TISSUE LEVELS OF KLOTHO AND TNF-α

Yıl 2024, , 117 - 123, 04.06.2024

Mehmet Deniz Yener , Tuncay Çolak , Esra Acar , Fatma Ceyla Eraldemir

https://doi.org/10.26650/JARHS2024-1375216

Öz

Objective: Chronic stress is recognized as a factor that affects almost all organs and tissues and disrupts homeostasis. Stress also directly impacts the inflammatory process. In addition, klotho is a protein associated with lifespan. This study investigates the relationship that chronic stress has with klotho and tumor necrosis factor alpha (TNF-α), which is a key protein in the proinflammatory process.

Materials and Methods: The study involves 16 Wistar albino rats divided into control and stress groups. The study applies the protocol for the chronic unpredictable mild stress (CUMS) model and uses the enzymelinked immunosorbent assay (ELISA) method to measure the TNF-α and Klotho levels in the serum, heart, aorta, and liver tissues.

Results: The serum samples obtained from the stress group were found to have a significant decrease in klotho levels (p=0.013) and high TNF-α levels (p=0.042). However, no significant difference was observed in the TNF-α or klotho levels in the heart, aorta, and liver tissues between groups.

Conclusion: Under chronic stress, a significant increase is observed in TNFα, one of the main cytokines of inflammation, as well as a decrease in klotho hormone. This research endeavors to contribute to the existing body of knowledge concerning the interplay among stress, inflammation, and longevity.

Anahtar Kelimeler

Chronic stress, inflammation, klotho, TNF-α

Proje Numarası

0742018

KRONİK STRESİN KLOTHO VE TNF-α’NIN SERUM VE DOKU SEVİYELERİ ÜZERİNE ETKİSİ

Öz

Amaç: Kronik stres hemen hemen tüm organları/dokuları etkileyen ve homeostazı bozan bir faktör olarak kabul edilmektedir. Stres, enflamatuar süreç üzerinde doğrudan bir etkiye sahiptir. Bununla birlikte, Klotho yaşam süresi ile ilişkili bir proteindir. Çalışmamızda kronik stres ile proinflamatuar süreçte anahtar bir protein olan Tümör nekroz faktör alfa (TNF-α) ve Klotho arasındaki ilişkiyi araştırdık.

Gereç ve Yöntemler: Çalışmamız kontrol ve stres gruplarına ayrılan 16 Wistar albino’dan oluşmuştur. Kronik öngörülemeyen hafif stres model protokolü uygulandı. Serum, kalp, aort ve karaciğer dokusundaki TNF-α ve Klotho düzeyleri ELISA yöntemi kullanılarak ölçüldü.

Bulgular: Stres grubundan alınan serum örneklerinin Klotho düzeylerinde anlamlı azalma (p=0,013), TNF-α düzeylerinde ise anlamlı yükseliş (p=0,042) olduğu belirlendi. Ancak; gruplar arasında kalp, aort ve karaciğer dokularındaki TNF-α ve Klotho düzeylerinde anlamlı bir fark gözlenmedi.

Sonuç: Kronik stres altında inflamasyonun ana sitokinlerinden biri olan TNF-α’ da belirgin bir artış, Klotho hormonunda ise azalma gözlendi. Araştırmamız; stres, iltihaplanma ve uzun ömür arasındaki etkileşime ilişkin mevcut bilgi birikimine katkıda bulunmaya çalışmaktadır

Anahtar Kelimeler

Kronik stres, inflamasyon, Klotho, TNF-α

Proje Numarası

0742018

Kaynakça

• Cannon WB. Stresses and strains of homeostasis. AJMS 1935;189(1):13-4. google scholar
• Lu S, Wei F, Li G. The evolution of the concept of stress and the framework of the stress system. CES 2021;5(6):76-85. google scholar
• Maes M, Song C, Lin A, De Jongh R, Van Gastel A, Kenis G, et al. The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine 1998;10(4):313-8. google scholar
• Steptoe A, Hamer M, Chida Y. The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun 2007;21(7):901-12. google scholar
• Ren J, Sowers JR, Zhang Y. Metabolic stress, autophagy and cardiovascular aging: From pathophysiology to therapeutics. Trends Endocrinol Metab 2018;29(10):699-711. google scholar
• Herman JP, McKlveen JM, Ghosal S, Kopp B, Wulsin A. Makinson R, et al. Regulation of the hypothalamic-pituitary-adrenocortical stress response. Compr Physiol 2016;6(2):603-21. google scholar
• Tan SY, Yip A. Hans Selye (1907-1982): Founder of the stress theory. Singapore Med J 2018;59(4):170-1. google scholar
• Liu YZ, Wang YX, Jiang CL. Inflammation: The common pathway of stress-related diseases. Front Hum Neurosci 2017;11:316. google scholar
• Koo JW, Russo SJ, Ferguson D, Nestler EJ, Duman RS. Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and depressive behavior. Proc Natl Acad Sci USA 2010;107(6):2669-74. google scholar
• Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997;390(6655):45-51. google scholar
• Prud’homme GJ, Kurt M, Wang Q. Pathobiology of the klotho antiaging protein and therapeutic considerations. Front Aging 2022;3:931331. google scholar
• Olauson H, Vervloet MG, Cozzolino M, Massy ZA, Urena Torres P, Larsson TE. New insights into the FGF23-Klotho axis. Semin Nephrol 2014;34(6):586-97. google scholar
• Amaro-Gahete FJ, de-la-O A, Jurado-Fasoli L, Ruiz JR, Castillo MJ, Gutierrez Â. Role of exercise on s-klotho protein regulation: A systematic review. Curr Aging Sci 2018;11(2):100-7. google scholar
• Xu Y, Sun Z. Molecular basis of klotho: From gene to function in aging. Endocr Rev 2015;36(2):174-93. google scholar
• Kuro-O M. The FGF23 and klotho system beyond mineral metabolism. Clin Exp Nephrol 2017;21(1):64-9. google scholar
• Prather AA, Epel ES, Arenander J, Broestl L, Garay BI, Wang D, et al. Longevity factor klotho and chronic psychological stress. Transl Psychiatry 2015;5(6):e585. google scholar
• Lee J, Kim D, Lee H jung, Choi JY, Min JY, Min KB. Association between serum klotho levels and cardiovascular disease risk factors in older adults. BMC Cardiovasc Disord 2022;22(1):442. google scholar
• Yamamoto M, Clark JD, Pastor JV, Gurnani P, Nandi A, Kurosu H, et al. Regulation of oxidative stress by the anti-aging hormone klotho. J Biol Chem 2005;280(45):38029-34. google scholar
• Maekawa Y, Ishikawa K, Yasuda O, Oguro R, Hanasaki H, Kida I, et al. Klotho suppresses TNF-a-induced expression of adhesion molecules in the endothelium and attenuates NF-kappaB activation. Endocrine 2009;35(3):341-6. google scholar
• Mitobe M, Yoshida T, Sugiura H, Shirota S, Tsuchiya K, Nihei H. Oxidative stress decreases klotho expression in a mouse kidney cell line. Nephron Exp Nephrol 2005;101(2):e67-74. google scholar
• D^az-Delf^n J, Hondares E, Iglesias R, Giralt M, Caelles C, Villarroya F. TNF-a represses Ş-Klotho expression and impairs FGF21 action in adipose cells: Involvement of JNK1 in the FGF21 pathway. Endocrinology 2012;153(9):4238-45. google scholar
• Willner P, Towell A, Sampson D, Sophokleous S, Muscat R. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology 1987;93(3):358-64. google scholar
• Matuszewich L, McFadden LM, Friedman RD, Frye CA. Neurochemical and behavioral effects of chronic unpredictable stress. Behav Pharmacol 2014;25(5-6):557-66. google scholar
• Hartree EF. Determination of protein: A modification of the lowry method that gives a linear photometric response. Anal Biochem 1972;48(2):422-7. google scholar
• Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Ischemia/Reperfusion. Compr Physiol 2016;7(1):113-70. google scholar
• Miller AH, Maletic V, Raison CL. Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biol Psychiatry 2009;65(9):732-41. google scholar
• Harsanyi S, Kupcova I, Danisovic L, Klein M. Selected biomarkers of depression: What are the effects of cytokines and inflammation? Int J Mol Sci 2022;24(1):578. google scholar
• Alqurashi GK, Hindi EA, Zayed MA, Abd El-Aziz GS, Alturkistani HA, Ibrahim RF, et al. The impact of chronic unpredictable mild stress-induced depression on spatial, recognition and reference memory tasks in mice: Behavioral and histological study. Behav Sci 2022;12(6):166. google scholar
• Yang H, Tracey KJ. Targeting HMGB1 in inflammation. BBA 2010;1799(1):149-56. google scholar
• Huang D, Wang S. Association between the anti-aging protein klotho and sleep duration in general population. Int J Gen Med 2021;14:10023-30. google scholar
• Wu HJ, Wu WN, Fan H, Liu LE, Zhan JQ, Li YH, et al. Life extension factor klotho regulates behavioral responses to stress via modulation of GluN2B function in the nucleus accumbens. Neuropsychopharmacology 2022;47(9):1710-20. google scholar