SRXN1 is a novel protective factor against methylmercury-induced apoptosis in C17.2 mouse neural stem cells.

Methylmercury is an environmental pollutant that exhibits severe cerebral neurotoxicity and remains a worldwide problem. Motor and mental development disorders have been observed in children born to women who consumed relatively large amounts of methylmercury via contaminated fish during pregnancy. We previously found by RNA-sequencing analysis that treatment of C17.2 mouse neural stem cells with methylmercury induced the expression of SRXN1 (sulfiredoxin-1), a redox regulator. In this study, we examined the effect of methylmercury on SRXN1 expression and the role of SRXN1 in methylmercury-induced cell death. After C17.2 cells were treated with methylmercury, both mRNA and protein expression of SRXN1 increased in a time- and concentration-dependent manner. Because the induction of SRXN1 expression by methylmercury was suppressed by pretreatment with a transcription inhibitor, we searched the upstream region of the SRXN1 gene and found a binding sequence for transcription factor 3 (TCF3). Interestingly, the induction of SRXN1 expression by methylmercury was attenuated in cells in which TCF3 expression was suppressed by siRNA compared with control cells. This suggests that TCF3 is involved in the induction of SRXN1 expression by methylmercury. We previously reported that TCF3 overexpression suppressed methylmercury-induced apoptosis; in the present study, we found that SRXN1 overexpression also suppressed methylmercury-induced apoptosis, as assessed by cleaved caspase-3 expression. In summary, our results indicate that SRXN1 induced by TCF3-mediated expression is a novel protective factor against methylmercury-induced apoptosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43188-024-00277-6.