文献类型： 外文期刊

作者： Chu, Bing-Xin ¹ ; Fan, Rui-Feng ¹ ; Lin, Shu-Qian ¹ ; Yang, Du-Bao ¹ ; Wang, Zhen-Yong ¹ ; Wang, Lin ¹ ;

作者机构： 1.Shandong Agr Univ, Coll Anim Sci & Vet Med, 61 Daisong St, Tai An 271018, Shandong, Peoples R China

2.Shandong Agr Univ, Shandong Prov Key Lab Anim Biotechnol & Dis Contr, 61 Daisong St, Tai An 271018, Shandong, Peoples R China

3.Shandong Agr Univ, Shandong Prov Engn Technol Res Ctr Anim Dis Contr, 61 Daizong St, Tai An 271018, Shandong, Peoples R China

4.Shandong Acad Agr Sci, Inst Poultry Sci, Jinan 250023, Shandong, Peoples R China

关键词： Lead(II); Autophagy; Apoptosis; Cytotoxicity; Proximal tubular cells

期刊名称：JOURNAL OF INORGANIC BIOCHEMISTRY （ 影响因子：4.155； 五年影响因子：3.613 ）

ISSN： 0162-0134

年卷期： 2018 年 182 卷

页码：

收录情况： SCI

摘要： 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(H) 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(H)-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(H)induced nephrotoxicity.