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) 是一种潜在有毒的化学元素，在环境中大量存在。我们之前报道过锑通过活性氧依赖性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）在锑诱导的神经元损伤中的作用。我们发现Sb处理在体外和体内均诱导CREB磷酸化和神经元凋亡。有趣的是，用 666−15 抑制 CREB ​​的转录活性可通过下调 B 细胞淋巴瘤 2 (Bcl-2) 显着增强 PC12 细胞的凋亡。此外，Sb 还激活 ERK、JNK 和 p38 信号传导；然而，只有 JNK 促进 CREB ​​磷酸化。总之，我们的研究结果表明 JNK 磷酸化 CREB​​通过上调 Bcl-2 减弱 Sb 诱导的神经元凋亡。这些数据表明，JNK 依赖性 CREB ​​激活可防止神经元发生 Sb 诱导的细胞凋亡，并指导开发新策略来预防 Sb 诱导的神经毒性。