Seol Ayun, Kim Ji Eun, Song Hee Jin, Kim Tae Ryeol, Park Eun Seo, Park Ki Ho, Lim Su Jeong, Wang Su Ha, Park Seong Cheol, Choi Youngwoo, Kim Hyesung, Seo Sungbaek, Hwang Dae Youn
Department of Biomaterials Science (BK21 FOUR Program)/Life and Industry Convergence Research Institute, College of Natural Resources and Life Science, Pusan National University, Korea.
Department of Nanomechatronics Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Korea.
J Toxicol Sci. 2025;50(7):361-378. doi: 10.2131/jts.50.361.
The internalization mechanism of microplastics (MPs) into human cells has attracted considerable attention because these mechanisms are closely related to the physical and chemical properties of MPs. This study examined the response of human colon cells to autophagy, ER stress, and inflammation during the regulation on the internalization of polystyrene (PS)-MPs (0.4-0.6 μm size). To achieve this, changes in their key markers were analyzed in MPs-treated SNU-1826 cells after a cotreatment with uptake inhibitors or stimulators. The internalization of MPs was significantly higher in SNU-1826 cells than in other cells originated from differential tissues, such as the small intestine, kidneys, and nerves. On the other hand, the internalization of MPs into SNU-1826 cells was suppressed by cytochalasin D (CD) but not by pitstop (Pt). During this inhibition, the levels of the key parameters for autophagy (Light Chain 3-I/II (LC3-I/II) and Beclin1), ER stress (eukaryotic translation initiation factor 2 subunit alpha (EIF2α) and inositol-requiring kinase 1 alpha (IRE1α)), and inflammation (inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6) were suppressed in MPs+CD-treated SNU-1826 cells. In addition, the internalization of MPs into SNU-1826 cells was stimulated by a ZnSO treatment, not by CaCl. These stimulation effects were reflected in the alteration of the critical parameters for autophagy, ER stress, and inflammation. Furthermore, the positive correlation was detected between MPs internalization and most parameters for cellular responses although their inhibition is stronger than stimulation. These results suggest that the internalization of MPs into SNU-1826 cells may be strongly associated with the changes in autophagy, ER stress, and inflammation during the regulation of CD and ZnSO.
微塑料（MPs）进入人体细胞的内化机制备受关注，因为这些机制与微塑料的物理和化学性质密切相关。本研究检测了人结肠细胞在聚苯乙烯（PS）- MPs（尺寸为0.4 - 0.6μm）内化调控过程中对自噬、内质网应激和炎症的反应。为此，在用摄取抑制剂或刺激剂共处理后，分析了MPs处理的SNU - 1826细胞中其关键标志物的变化。MPs在SNU - 1826细胞中的内化显著高于源自不同组织（如小肠、肾脏和神经）的其他细胞。另一方面，细胞松弛素D（CD）可抑制MPs进入SNU - 1826细胞，而垂体后叶素（Pt）则无此作用。在此抑制过程中，MPs + CD处理的SNU - 1826细胞中自噬（轻链3 - I/II（LC3 - I/II）和Beclin1）、内质网应激（真核翻译起始因子2亚基α（EIF2α）和肌醇需求激酶1α（IRE1α））以及炎症（诱导型一氧化氮合酶（iNOS）、环氧化酶2（COX - 2）、肿瘤坏死因子α（TNF - α）和白细胞介素（IL）- 6）的关键参数水平均受到抑制。此外，硫酸锌（ZnSO）处理可刺激MPs进入SNU - 1826细胞，而氯化钙（CaCl）则无此作用。这些刺激作用反映在自噬、内质网应激和炎症关键参数的改变上。此外，尽管MPs内化的抑制作用强于刺激作用，但仍检测到MPs内化与大多数细胞反应参数之间存在正相关。这些结果表明，MPs进入SNU - 1826细胞的内化过程可能与CD和ZnSO调控期间自噬、内质网应激和炎症的变化密切相关。
