Autophagy and apoptosis are two different biological processes that determine cell fates. We previously reported that autophagy inhibition and apoptosis induction are involved in lead(II)-induced cytotoxicity in primary rat proximal tubular (rPT) cells, but the interplay between them remains to be elucidated. Firstly, data showed that lead(II)-induced elevation of LC3-II protein levels can be significantly modulated by 3-methyladenine or rapamycin; moreover, protein levels of Autophagy-related protein 5 (Atg5) and Beclin-1 were markedly up-regulated by lead(II) treatment, demonstrating that lead(II) could promote the autophagosomes formation in rPT cells. Next, we applied three pharmacological agents and genetic method targeting the early stage of autophagy to validate that enhancement of autophagosomes formation can inhibit lead(II)-induced apoptotic cell death in rPT cells. Simultaneously, lead(II) inhibited the autophagic degradation of rPT cells, while the addition of autophagic degradation inhibitor bafilomycin A1 aggravated lead(II)-induced apoptotic death in rPT cells. Collectively, this study provided us a good model to know about the dynamic process of lead(II)-induced autophagy in rPT cells, and the interplay between autophagy and apoptosis highlights a new sight into the mechanism of lead(II)-induced nephrotoxicity.

自噬和凋亡是决定细胞命运的两个不同的生物学过程。我们先前曾报道自噬抑制和凋亡诱导与铅（II）诱导的原代大鼠近端肾小管（rPT）细胞的细胞毒性有关，但它们之间的相互作用尚待阐明。首先，数据表明，铅（II）诱导的LC3-II蛋白水平升高可被3-甲基腺嘌呤或雷帕霉素显着调节。此外，铅（II）处理显着上调了自噬相关蛋白5（Atg5）和Beclin-1的蛋白水平，表明铅（II）可以促进rPT细胞中自噬体的形成。下一个，我们应用了针对自噬早期阶段的三种药理学和遗传方法来验证自噬体形成的增强可以抑制铅（II）诱导的rPT细胞凋亡。同时，铅（II）抑制了rPT细胞的自噬降解，而添加自噬降解抑制剂bafilomycin A1加剧了铅（II）诱导的rPT细胞凋亡。总的来说，这项研究为我们提供了一个很好的模型来了解rPT细胞中铅（II）诱导的自噬的动态过程，并且自噬与凋亡之间的相互作用突显了对铅（II）诱导的肾毒性机制的新认识。而自噬降解抑制剂巴氟霉素A1的添加会加剧铅（II）诱导的rPT细胞凋亡。总的来说，这项研究为我们提供了一个很好的模型来了解rPT细胞中铅（II）诱导的自噬的动态过程，并且自噬与凋亡之间的相互作用突显了对铅（II）诱导的肾毒性机制的新认识。而自噬降解抑制剂巴氟霉素A1的添加会加剧铅（II）诱导的rPT细胞凋亡。总的来说，这项研究为我们提供了一个很好的模型来了解rPT细胞中铅（II）诱导的自噬的动态过程，并且自噬与凋亡之间的相互作用突显了对铅（II）诱导的肾毒性机制的新认识。