Zebrafish, a Novel Model System to Study Uremic Toxins: The Case for the Sulfur Amino Acid Lanthionine

International Journal of Molecular Sciences

Evgeniya Anishchenko¹  Miriam Zacchia¹  Salvatore D’Aniello¹  Carmela Vigorito²  AlessandraF. Perna²  Francesco Trepiccione²  Diego Ingrosso² 

[1] Respiratory Sciences, University of Campania “Luigi Vanvitelli”, School of Medicine, via Pansini 5, Bldg 17, 80131 Naples, Italy;;First Division of Nephrology, Department of Cardiotoracic &

关键词: uremic toxin;    lanthionine;    uremia;    dialysis;    cardiovascular disease;    zebrafish;    glutathione;   

DOI  :  10.3390/ijms19051323

来源: DOAJ

【 摘 要 】

The non-proteinogenic amino acid lanthionine is a byproduct of hydrogen sulfide biosynthesis: the third endogenous vasodilator gas, after nitric oxide and carbon monoxide. While hydrogen sulfide is decreased in uremic patients on hemodialysis, lanthionine is increased and has been proposed as a new uremic toxin, since it is able to impair hydrogen sulfide production in hepatoma cells. To characterize lanthionine as a uremic toxin, we explored its effects during the early development of the zebrafish (Danio rerio), a widely used model to study the organ and tissue alterations induced by xenobiotics. Lanthionine was employed at concentrations reproducing those previously detected in uremia. Light-induced visual motor response was also studied by means of the DanioVision system. Treatment of zebrafish embryos with lanthionine determined acute phenotypical alterations, on heart organogenesis (disproportion in cardiac chambers), increased heart beating, and arrhythmia. Lanthionine also induced locomotor alterations in zebrafish embryos. Some of these effects could be counteracted by glutathione. Lanthionine exerted acute effects on transsulfuration enzymes and the expression of genes involved in inflammation and metabolic regulation, and modified microRNA expression in a way comparable with some alterations detected in uremia. Lanthionine meets the criteria for classification as a uremic toxin. Zebrafish can be successfully used to explore uremic toxin effects.

【 授权许可】

Unknown