Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, 210009, China.
Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, 210009, China.
J Hazard Mater. 2020 Jul 15;394:122439. doi: 10.1016/j.jhazmat.2020.122439. Epub 2020 Mar 2.
Ambient particulate matter (APM) is becoming a global environmental problem that seriously jeopardizes public health. Previous evidence hinted that APM correlates to cardiovascular diseases. As a potential target, equilibrium of endothelial cell is a prerequisite for vascular health which could be vulnerably attacked by particles, but the specific mechanisms whereby APM damages endothelial cells have not been fully elucidated. In the current study, based on two classical mechanisms of oxidative stress and intracellular calcium overload, we aimed to explore their roles in APM-induced endothelial cell apoptosis from the perspective of subcellular levels, including endoplasmic reticulum (ER) stress and mitochondrial dysfunction. As a result, PM SRM1648a results in oxidative stress and calcium overload in EA.hy926 cells. Additionally, ERs and mitochondria could be severely disturbed by particles in morphology and function, characterized by swelling ERs, mitochondrial fission and disappearance of cristae, coupled with ER damage, mtROS overproduction and significant reduction in mitochondrial membrane potential (MMP). Adverse effects on these organelles are the prime culprits of following apoptosis in endothelial cells. Fortunately, additional antioxidants and calcium inhibitors could mitigate cellular lesion through improvement of subcellular function. Intriguingly, antioxidants relieve cell stress via both mitochondrial and ER stress-mediated pathways, whereas the role of calcium modulators in cell apoptosis is independent of the mitochondrial pathway but could be explained by amelioration of ER stress. In conclusion, our data basically revealed that internalized PM SRM1648a triggers oxidative stress and calcium influx in EA.hy926 endothelial cells, followed by multiple subcellular damage and eventually contributes to cell death, during which antioxidants and calcium inhibitors confer protective effects.
环境细颗粒物（APM）正成为一个全球性的环境问题，严重威胁着公众健康。先前的证据表明，APM 与心血管疾病有关。作为一个潜在的靶点，内皮细胞的平衡是血管健康的前提，它可能容易受到颗粒的攻击，但 APM 损伤内皮细胞的具体机制尚未完全阐明。在本研究中，基于氧化应激和细胞内钙超载的两个经典机制，我们旨在从亚细胞水平探讨它们在 APM 诱导内皮细胞凋亡中的作用，包括内质网（ER）应激和线粒体功能障碍。结果表明，PM SRM1648a 可导致 EA.hy926 细胞发生氧化应激和钙超载。此外，颗粒可严重破坏 ER 和线粒体的形态和功能，表现为 ER 肿胀、线粒体裂变和嵴消失，同时伴有 ER 损伤、mtROS 产生过多和线粒体膜电位（MMP）显著降低。这些细胞器的损伤是内皮细胞随后发生凋亡的主要原因。幸运的是，额外的抗氧化剂和钙抑制剂可以通过改善亚细胞功能来减轻细胞损伤。有趣的是，抗氧化剂通过线粒体和 ER 应激介导的途径缓解细胞应激，而钙调节剂在细胞凋亡中的作用不依赖于线粒体途径，而是可以通过改善 ER 应激来解释。总之，我们的数据基本揭示了内吞的 PM SRM1648a 在内皮细胞 EA.hy926 中引发氧化应激和钙内流，随后引发多种亚细胞损伤，最终导致细胞死亡，而抗氧化剂和钙抑制剂具有保护作用。
