Klotho Protein Contributes to Cardioprotection During Ischaemia/reperfusion Injury

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2020 Apr 23

PMID 32319182

Citations 13

Authors

Agnieszka Olejnik

Anna Krzywonos-Zawadzka

Marta Banaszkiewicz

Iwona Bil-Lula

Affiliations

Soon will be listed here.

Abstract

Restoration of blood flow to ischaemic heart inflicts ischaemia/reperfusion (I/R) injury, which manifests in metabolic and morphological disorders. Klotho is a protein with antioxidative and antiapoptotic activity, and is involved in the regulation of inflammation and fibrosis. The aim of the current research was to determine the role of Klotho in the heart subjected to I/R injury, as well as to study Klotho as a potential cardioprotective agent. Human cardiomyocytes and Wistar rat hearts perfused using Langendorff method subjected to I/R have been used. Hemodynamic parameters of heart function, markers of I/R injury, and gene and protein expression of Klotho were measured. Human cardiomyocytes were also incubated in the presence of recombinant Klotho protein, and the viability of cells was measured. There was a higher expression of Klotho gene and protein synthesis in the cardiomyocytes subjected to I/R injury. The compensatory production and release of Klotho protein from cardiac tissue during I/R were also shown. The treatment of cardiomyocytes subjected to I/R with Klotho protein resulted in increased viability and metabolic activity of cells. Thus, Klotho contributes to compensatory mechanism during I/R, and could be used as a marker of injury and as a potential cardiopreventive/cardioprotective agent.

Citing Articles

Study on the Synergistic Effect of Klotho and KRAS on Reducing Ferroptosis After Myocardial Infarction by Regulating RAP1/ERK Signaling Pathway.

Cai C, Wu Y, Feng X, Ye X, Liu P, Huang X Appl Biochem Biotechnol. 2025; .

PMID: 39808407 DOI: 10.1007/s12010-024-05171-3.

Mixture of Doxycycline, ML-7 and L-NAME Restores the Pro- and Antioxidant Balance during Myocardial Infarction-In Vivo Pig Model Study.

Bil-Lula I, Kuliczkowski W, Krzywonos-Zawadzka A, Frydrychowski P, Stygar D, Halucha K Biomedicines. 2024; 12(4).

PMID: 38672140 PMC: 11047935. DOI: 10.3390/biomedicines12040784.

Gene Therapy Strategies Targeting Aging-Related Diseases.

Yu J, Li T, Zhu J Aging Dis. 2023; 14(2):398-417.

PMID: 37008065 PMC: 10017145. DOI: 10.14336/AD.2022.00725.

The impact of SGLT2 inhibitors on αKlotho in renal MDCK and HK-2 cells.

Wolf L, Foller M, Feger M Front Endocrinol (Lausanne). 2023; 14:1069715.

PMID: 36967770 PMC: 10032406. DOI: 10.3389/fendo.2023.1069715.

Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury.

Gonzalez-Lafuente L, Navarro-Garcia J, Valero-Almazan A, Rodriguez-Sanchez E, Vazquez-Sanchez S, Mercado-Garcia E Int J Mol Sci. 2023; 24(2).

PMID: 36674838 PMC: 9867237. DOI: 10.3390/ijms24021322.

References

Zhao Z, Vinten-Johansen J . Postconditioning: reduction of reperfusion-induced injury. Cardiovasc Res. 2006; 70(2):200-11. DOI: 10.1016/j.cardiores.2006.01.024. View

Zhou X, Wang X . Klotho: a novel biomarker for cancer. J Cancer Res Clin Oncol. 2014; 141(6):961-9. DOI: 10.1007/s00432-014-1788-y. View

Semba R, Cappola A, Sun K, Bandinelli S, Dalal M, Crasto C . Plasma klotho and cardiovascular disease in adults. J Am Geriatr Soc. 2011; 59(9):1596-601. PMC: 3486641. DOI: 10.1111/j.1532-5415.2011.03558.x. View

Sugiura H, Yoshida T, Tsuchiya K, Mitobe M, Nishimura S, Shirota S . Klotho reduces apoptosis in experimental ischaemic acute renal failure. Nephrol Dial Transplant. 2005; 20(12):2636-45. DOI: 10.1093/ndt/gfi165. View

Hu M, Shi M, Gillings N, Flores B, Takahashi M, Kuro-O M . Recombinant α-Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy. Kidney Int. 2017; 91(5):1104-1114. PMC: 5592833. DOI: 10.1016/j.kint.2016.10.034. View

Cararo-Lopes M, Mazucanti C, Scavone C, Kawamoto E, Berwick D . The relevance of α-KLOTHO to the central nervous system: Some key questions. Ageing Res Rev. 2017; 36:137-148. DOI: 10.1016/j.arr.2017.03.003. View

Schnedl W, Mikelsaar A, Breitenbach M, DANN O . DIPI and DAPI: fluorescence banding with only negliglible fading. Hum Genet. 1977; 36(2):167-72. DOI: 10.1007/BF00273255. View

Fan J, Sun Z . The Antiaging Gene Klotho Regulates Proliferation and Differentiation of Adipose-Derived Stem Cells. Stem Cells. 2016; 34(6):1615-25. PMC: 5266740. DOI: 10.1002/stem.2305. View

Fudge D, Russell D, Beriault D, Moore W, Lane E, Vogl A . The intermediate filament network in cultured human keratinocytes is remarkably extensible and resilient. PLoS One. 2008; 3(6):e2327. PMC: 2390850. DOI: 10.1371/journal.pone.0002327. View

10.

Sugiura H, Yoshida T, Mitobe M, Yoshida S, Shiohira S, Nitta K . Klotho reduces apoptosis in experimental ischaemic acute kidney injury via HSP-70. Nephrol Dial Transplant. 2009; 25(1):60-8. DOI: 10.1093/ndt/gfp451. View

11.

Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T . Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997; 390(6655):45-51. DOI: 10.1038/36285. View

12.

Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y . Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun. 1998; 242(3):626-30. DOI: 10.1006/bbrc.1997.8019. View

13.

Krzywonos-Zawadzka A, Franczak A, Olejnik A, Radomski M, Gilmer J, Sawicki G . Cardioprotective effect of MMP-2-inhibitor-NO-donor hybrid against ischaemia/reperfusion injury. J Cell Mol Med. 2019; 23(4):2836-2848. PMC: 6433672. DOI: 10.1111/jcmm.14191. View

14.

Kumar A, Cannon C . Acute coronary syndromes: diagnosis and management, part I. Mayo Clin Proc. 2009; 84(10):917-38. PMC: 2755812. DOI: 10.4065/84.10.917. View

15.

Yang K, Wang C, Nie L, Zhao X, Gu J, Guan X . Klotho Protects Against Indoxyl Sulphate-Induced Myocardial Hypertrophy. J Am Soc Nephrol. 2015; 26(10):2434-46. PMC: 4587686. DOI: 10.1681/ASN.2014060543. View

16.

Qian Y, Guo X, Che L, Guan X, Wu B, Lu R . Klotho Reduces Necroptosis by Targeting Oxidative Stress Involved in Renal Ischemic-Reperfusion Injury. Cell Physiol Biochem. 2018; 45(6):2268-2282. DOI: 10.1159/000488172. View

17.

Guo Y, Zhuang X, Huang Z, Zou J, Yang D, Hu X . Klotho protects the heart from hyperglycemia-induced injury by inactivating ROS and NF-κB-mediated inflammation both in vitro and in vivo. Biochim Biophys Acta Mol Basis Dis. 2017; 1864(1):238-251. DOI: 10.1016/j.bbadis.2017.09.029. View

18.

Lin Y, Sun Z . In vivo pancreatic β-cell-specific expression of antiaging gene Klotho: a novel approach for preserving β-cells in type 2 diabetes. Diabetes. 2014; 64(4):1444-58. PMC: 4375073. DOI: 10.2337/db14-0632. View

19.

Arking D, Becker D, Yanek L, Fallin D, Judge D, Moy T . KLOTHO allele status and the risk of early-onset occult coronary artery disease. Am J Hum Genet. 2003; 72(5):1154-61. PMC: 1180268. DOI: 10.1086/375035. View

20.

Aizawa H, Saito Y, Nakamura T, Inoue M, Imanari T, Ohyama Y . Downregulation of the Klotho gene in the kidney under sustained circulatory stress in rats. Biochem Biophys Res Commun. 1998; 249(3):865-71. DOI: 10.1006/bbrc.1998.9246. View