Antimony (Sb) is a potentially toxic chemical element abundantly found in the environment. We previously reported that Sb promoted neuronal deathvia reactive oxygen species-dependent autophagy. Here, we assessed the role of cyclic adenosine monophosphate response element-binding protein (CREB) in Sb-induced neuronal damage. We found that Sb treatment induced CREB phosphorylation and neuronal apoptosis both in vitro and in vivo. Interestingly, inhibition of CREB’s transcriptional activity with 666−15 dramatically enhanced apoptosis in PC12 cells by downregulating B-cell lymphoma 2 (Bcl-2). Additionally, Sb activated ERK, JNK, and p38 signaling ; however, only JNK promoted CREB phosphorylation. In conclusion, our findings suggest that CREB phosphorylation by JNK attenuates Sb-induced neuronal apoptosis via Bcl-2 upregulation. These data suggest that JNK-dependent CREB activation prevents neurons from Sb-induced apoptosis and guides the development of novel strategies to prevent Sb-induced neurotoxicity.

锑 (Sb) 是一种广泛存在于环境中的潜在有毒化学元素。我们之前报道过 Sb 通过依赖活性氧的自噬促进神经元死亡。在这里，我们评估了环磷酸腺苷反应元件结合蛋白 (CREB) 在 Sb 诱导的神经元损伤中的作用。我们发现 Sb 处理在体外和体内诱导 CREB ​​磷酸化和神经元凋亡. 有趣的是，用 666-15 抑制 CREB ​​的转录活性通过下调 B 细胞淋巴瘤 2 (Bcl-2) 显着增强了 PC12 细胞的凋亡。此外，Sb 激活 ERK、JNK 和 p38 信号；然而，只有 JNK 促进了 CREB ​​磷酸化。总之，我们的研究结果表明 JNK 的 CREB ​​磷酸化通过Bcl-2 上调减弱了 Sb 诱导的神经元凋亡。这些数据表明，JNK 依赖性 CREB ​​激活可防止神经元免受 Sb 诱导的细胞凋亡，并指导开发防止 Sb 诱导的神经毒性的新策略。