TXNIP是一种对氧化条件敏感的蛋白质，其表达与癌症、糖尿病、缺血和神经退行性疾病等死亡进程相关。因此，许多研究提出TXNIP作为多种疾病的治疗靶点。小脑颗粒神经元暴露于丹参酮或低钾条件下会导致凋亡死亡。这两种条件都会产生早期的活性氧（ROS）生成，从而引起ASK1途径和凋亡机制的激活。在这些模型中，已经显示出ROS介导的TXNIP蛋白增加。在这里，我们评估了在神经元死亡期间调节Txnip表达的分子机制，以及蛋白质在这两种凋亡条件引起的细胞死亡进程中的作用。在培养的小脑颗粒神经元中，我们观察到低钾和丹参酮引起ROS的早期增加与Txnip mRNA的增加相关。当我们评估基因的启动子时，发现JASPAR报道的FOXO1/3转录因子结合位点靠近转录起始位点（TSS）。然后，我们通过染色质免疫共沉淀技术（ChIP）验证了FOXO3在低钾处理1小时后与Txnip启动子的相互作用。我们还通过低钾和丹参酮处理检测到FOXO3核定位。最后，通过在神经母细胞瘤MSN细胞系中使用shRNA，我们发现Txnip的下调减少了丹参酮刺激引起的神经元死亡。综上所述，这些结果表明ROS通过Akt抑制介导的FOXO3转录因子的激活促进Txnip的表达。我们还证明了TXNIP对神经元死亡进程的必要性。Copyright © 2023 García-Hernández and Morán.

TXNIP is a protein sensitive to oxidant conditions whose expression is related to the progression of death in cancer, diabetes, ischemia, and neurodegenerative diseases, among others. Because of this, many studies propose TXNIP as a therapeutic target in several diseases. Exposure of cerebellar granule neurons to staurosporine or low potassium leads to apoptotic death. Both conditions generate an early production of reactive oxygen species (ROS) that induces the activation of the ASK1 pathway and the apoptotic machinery. In these models, it has been shown an increase in TXNIP protein mediated by ROS. Here, we evaluated the molecular mechanisms involved in the regulation of the Txnip expression during neuronal death, as well as the role of the protein in the progression of cell death induced by these two apoptotic conditions. In cultured cerebellar granule neurons, we observed that low potassium and staurosporine induced an early increase in ROS that correlated with an increase in Txnip mRNA. When we evaluated the promoter of the gene, we found that the JASPAR-reported FOXO1/3 transcription factor motifs are close to the transcription start site (TSS). We then verified through the Chromatin immunoprecipitation technique (ChIP) that FOXO3 interacts with the Txnip promoter after 1 h of low potassium treatment. We also detected FOXO3 nuclear translocation by low potassium and staurosporine treatments. Finally, by using shRNA in the neuroblastoma MSN cell line, we found that Txnip downregulation decreased neuronal death induced by staurosporine stimulus. Together, these results suggest that ROS promotes the expression of Txnip through the activation of the FOXO3 transcription factor mediated by Akt inhibition. We also demonstrated that TXNIP is necessary for neuronal death progression.Copyright © 2023 García-Hernández and Morán.