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Title: Role of endogenous H2S in the attenuation of nickel-induced cell toxicity
Authors: Racine, Melanie
Keywords: nickel;H2S;cystathionine;gamma-lyase;fibroblasts;TGFβ1
Issue Date: 6-Jul-2018
Abstract: Nickel as a heavy metal is known to bring threat to human health, and its exposure is associated with changes in fibroblast activation which may contribute to its fibrotic properties. H2S has recently emerged as an important gasotransmitter involved in numerous cellular signal transduction and pathophysiological responses. Interaction of nickel and H2S on fibroblast cell activation has not yet been studied. Here, we showed that low dose nickel (200 μM) induced the activation of human fibroblast cells, as evidenced by 15% increase in cell growth, increased migration and higher expression of α-smooth muscle actin (αSMA) and fibronectin, while high dose of nickel (1 mM) inhibited cell viability. We further found that nickel repressed the mRNA and protein expression of cystathionine gamma-lyase (CSE, a H2S-generating enzyme) and blocked the endogenous production of H2S. Exogenously applied NaHS (a H2S donor) had no effect on nickel-induced cell viability but significantly attenuated nickel-stimulated cell migration and the expression of αSMA and fibronectin. In contrast, CSE deficiency deteriorated nickel-induced αSMA expression. Moreover, H2S incubation reversed nickel-stimulated TGFβ1/SMAD1 signal and blocked TGFβ1-initiated expressions of αSMA and fibronectin. Nickel inhibited the binding of Sp1 with CSE promoter but strengthened the binding of Sp1 with TGFβ1 promoter, which was reversed by exogenously applied NaHS. These data reveal that H2S protects from nickel-stimulated fibroblast activation and the CSE/H2S system can be a potential target for the treatment of tissue fibrosis induced by heavy metal.
Appears in Collections:Chemical Sciences - Master's Theses
Master's Theses

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