Down-regulation of S100A9 and S100A10 in manganese-resistant RBL-2H3 cells

Abstract

Exposure to excess amounts of manganese causes toxic effects, including neurological symptoms such as Parkinsonism. However, endogenous factors involved in the protection against manganese toxicity remain unclear. Previously, we showed that rat basophilic leukemia RBL-2H3 cells are highly sensitive to MnCl₂ compared with other rat cell lines. To identify the genes involved in resistance to manganese toxicity, two lines of Mn-resistant cells showing resistance to 300 µM MnCl₂ (RBL-Mnr300) and 1200 µM MnCl₂ (RBL-Mnr1200) were developed from RBL-2H3 cells by a stepwise increase in MnCl₂ concentration in the medium. Microarray analyses were carried out to compare gene expression between parental RBL-2H3 cells and RBL-Mnr300 or RBL-Mnr1200 cells. Five genes exhibited more than 10-fold up-regulation in both RBL-Mnr300 and RBL-Mnr1200 cells, and 24 genes exhibited less than 0.1-fold down-regulation in both Mn-resistant cell lines. The S100a9 and S100a10 genes, encoding the calcium-binding S100A9 and S100A10 proteins, respectively, were found among the three most down-regulated genes in both Mn-resistant cell lines. The marked decreases in mRNA levels of S100a9 and S100a10 were confirmed by real-time RT-PCR analyses. Further characterization and comparison of these Mn-resistant cells may enable the identification of novel genes that play important roles in the modification of manganese toxicity.

Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology

“…and metalloids. Such studies published these past three years in the Journal of Toxicological Sciences investigated the toxicity of many types of metals, including cadmium (Ohtani et al, 2013;Miura et al, 2013;Baba et al, 2014;Du et al, 2014;Park et al, 2015;Lukkhananan et al, 2015), mercury (Yoshida et al, 2013;Kim et al, 2014), methylmercury (Hwang et al, 2013a(Hwang et al, , 2013bIwai-Shimada et al, 2013;Chang et al, 2013;Hirooka et al, 2013;Kim et al, 2013;Watanabe et al, 2013;Shao et al, 2015;Toyama et al, 2015), aluminum (Zhang et al, 2013;Jinzhu et al, 2015), manganese (Fujishiro et al, 2013), uranium (Lestaevel et al, 2013), arsenic (Tokumoto et al, 2013;Wang et al, 2015), arsine (Kato et al, 2014), organic bismuth (Kohri et al, 2015), chromium (Kimura et al, 2015), and tributyltin (Oyanagi et al, 2015). Although methylmercury is one of the organic-inorganic hybrid molecules (the minimum unit!…”

Molecular and Neurochemical Mechanisms Dopamine Oxidation To O-Quinones in Parkinson’s Disease Pathogenesis

“…Manganese neurotoxicity has been associated with the impairment of dopaminergic neurons as a consequence of manganese accumulation in the dopaminergic neurons of the basal ganglia, particularly in the globus pallidus, causing extrapyramidal motor dysfunction [24]. Studies performed with manganese-resistant cells revealed that the calcium-binding proteins S100A9 and S100A10 are linked with manganese resistance in these cell lines [25]. Copper sulfate has been reported to catalyze dopamine oxidation, and high exposure to this metal in the mining industry has been associated with a Parkinsonism syndrome [26].…”