Department of Cardiology, the Affiliated Hospital of Southwest Medical University and Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory and Collaborative Innovation Center for the Prevention and Treatment of Cardiovascular Diseases of Sichuan Province, Institute of Cardiovascular Research, School of Basic Medical Science, Southwest Medical University, Luzhou, 646000, China.
Department of Cardiovascular Surgery, the Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, 646000, China.
Environ Sci Pollut Res Int. 2023 Nov;30(51):110579-110589. doi: 10.1007/s11356-023-30155-x. Epub 2023 Oct 4.
Polystyrene nanoplastics (PS-NPs) have recently been found to be present in human blood and kidney. However, the renal toxicity of PS-NPs and the underlying mechanisms have not been fully elucidated. Here, we found that exposure of PS-NPs induced apoptosis of human renal proximal tubular epithelial cells (HK-2) in a size- and dose-dependent manner as revealed by AnnexinV-FITC assay. In addition, PS-NPs promoted ROS production and caused structure changes of mitochondrial and endoplasmic reticulum. Mechanistically, transcriptional sequencing indicated the involvement of MAPK pathway in apoptosis, which was further confirmed by the upregulation of p-p38, p-ERK, CHOP, BAX, cytochrome C, and caspase 3 expression. This study clarified the molecular mechanism underlying PS-NP-induced apoptosis in HK-2 cells and contributed to our risk estimation of PS-NPs in human kidney.
聚苯乙烯纳米塑料 (PS-NPs) 最近被发现存在于人体血液和肾脏中。然而,PS-NPs 的肾毒性及其潜在机制尚未完全阐明。在这里,我们发现 PS-NPs 的暴露以大小和剂量依赖的方式诱导人肾近端肾小管上皮细胞 (HK-2) 的细胞凋亡,这通过 AnnexinV-FITC 检测得到证实。此外,PS-NPs 促进 ROS 产生,并导致线粒体和内质网结构变化。从机制上讲,转录测序表明 MAPK 通路参与细胞凋亡,这通过 p-p38、p-ERK、CHOP、BAX、细胞色素 C 和 caspase 3 表达的上调进一步得到证实。本研究阐明了 PS-NPs 诱导 HK-2 细胞凋亡的分子机制,有助于我们对 PS-NPs 对人体肾脏风险的评估。