Manganese(II) Chloride Alters Nucleotide and Nucleoside Catabolism in Zebrafish (Danio rerio) Adult Brain

Abstract

ATP and adenosine, the main signaling molecules of purinergic system, are involved in toxicological effects induced by metals. The manganese (Mn) exposure induces several cellular changes, which could interfere with signaling pathways, such as the purinergic system. In this study, we evaluated the effects of exposure to manganese(II) chloride (MnCl₂) during 96 h on nucleoside triphosphate diphosphohydrolase (NTPDase), ecto-5'-nucleotidase, and adenosine deaminase (ADA) activities, followed by analyzing the gene expression patterns of NTPDases (entpd1, entpd2a.1, entpd2a.2, entpd2-like, entpd3) and ADA (ADA ₁ , ADA _2.1 , ADA _2.2 , ADAasi, ADAL) families in zebrafish brain. In addition, the brain metabolism of nucleotides and nucleosides was evaluated after MnCl₂ exposure. The results showed that MnCl₂ exposure during 96 h inhibited the NTPDase (1.0 and 1.5 mM) and ecto-ADA (0.5, 1.0, and 1.5 mM) activities, further decreasing ADA2.1 expression at all MnCl₂ concentrations analyzed. Purine metabolism was also altered by the action of MnCl₂. An increased amount of ADP appeared at all MnCl₂ concentrations analyzed; however, AMP and adenosine levels are decreased at the concentrations of 1.0 and 1.5 mM MnCl₂, whereas decreased inosine (INO) levels were observed at all concentrations tested. The findings of this study demonstrated that MnCl₂ may inhibit NTPDase and ecto-ADA activities, consequently modulating nucleotide and nucleoside levels, which may contribute for the toxicological effects induced by this metal.

Keywords: Adenosine deaminase; Manganese(II) chloride; NTPDases; Purinergic signaling; Zebrafish.