Uremic Toxin Lanthionine Interferes with the Transsulfuration Pathway, Angiogenetic Signaling and Increases Intracellular Calcium

International Journal of Molecular Sciences

Luigi Mele¹  Rosanna Capasso²  Diego Ingrosso²  Carmela Vigorito³  Giovanna Capolongo³  Evgeniya Anishchenko³  Miriam Zacchia³  Patrizia Lombari³  AlessandraF. Perna³  Francesco Trepiccione³ 

[1] Department of Experimental Medicine, University of Campania “Luigi Vanvitelli,” 80138 Naples, Italy;Department of Precision Medicine, University of Campania “Luigi Vanvitelli,” 80138 Naples, Italy;Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli,” 80131 Naples, Italy;

关键词: lanthionine;    glutathione;    uremic toxin;    chronic kidney disease;    H₂S;    sulfane sulfur;    CBS;    CSE;    VEGFA;    calcium homeostasis;   

DOI  :  10.3390/ijms20092269

来源: DOAJ

【 摘 要 】

(1) The beneficial effects of hydrogen sulfide (H₂S) on the cardiovascular and nervous system have recently been re-evaluated. It has been shown that lanthionine, a side product of H₂S biosynthesis, previously used as a marker for H₂S production, is dramatically increased in circulation in uremia, while H₂S release is impaired. Thus, lanthionine could be classified as a novel uremic toxin. Our research was aimed at defining the mechanism(s) for lanthionine toxicity. (2) The effect of lanthionine on H₂S release was tested by a novel lead acetate strip test (LAST) in EA.hy926 cell cultures. Effects of glutathione, as a redox agent, were assayed. Levels of sulfane sulfur were evaluated using the SSP4 probe and flow cytometry. Protein content and glutathionylation were analyzed by Western Blotting and immunoprecipitation, respectively. Gene expression and miRNA levels were assessed by qPCR. (3) We demonstrated that, in endothelial cells, lanthionine hampers H₂S release; reduces protein content and glutathionylation of transsulfuration enzyme cystathionine-β-synthase; modifies the expression of miR-200c and miR-423; lowers expression of vascular endothelial growth factor VEGF; increases Ca²⁺ levels. (4) Lanthionine-induced alterations in cell cultures, which involve both sulfur amino acid metabolism and calcium homeostasis, are consistent with uremic dysfunctional characteristics and further support the uremic toxin role of this amino acid.

【 授权许可】

Unknown