Airborne fine particulate matter in Japan induces lipid synthesis and inhibits autophagy in HepG2 cells.
Airborne fine particulate matter in Japan induces lipid synthesis and inhibits autophagy in HepG2 cells.
复制标题
DOI：
10.1016/j.biocel.2021.106099
复制
发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Noriyoshi Ogino;Koichiro Miyagawa;Kenjiro Nagaoka;Kazuhiro Sumida;Masashi Kusanaga;Shinji Oe;Yuichi Honma;Michihiko Shibata;Masaru Harada;N. Suganuma;K. Ogino
中科院分区：
文献类型：
--
作者：
Noriyoshi Ogino;Koichiro Miyagawa;Kenjiro Nagaoka;Kazuhiro Sumida;Masashi Kusanaga;Shinji Oe;Yuichi Honma;Michihiko Shibata;Masaru Harada;N. Suganuma;K. Ogino
据报道，吸入直径小于2.5µm的颗粒物会加重脂肪肝疾病。然而，颗粒物质参与肝脏脂质代谢和自噬的成分和机制尚未完全阐明。我们发现日本的大气颗粒物即使在其脂质成分被去除后也会刺激肝细胞的脂肪生成。此外，我们证明了颗粒物质不促进自噬体的形成，但抑制肝细胞的自噬降解。在以前的毒性实验中，从大气中收集的颗粒物质通常含有来自过滤器的污染物。在这项研究中，我们将使用旋风和冲击器系统收集的含有较少污染物的粉状颗粒物质暴露于HepG2细胞，即人肝细胞。这种颗粒物质在HepG2细胞中诱导脂肪生成和内质网应激，以及之前在美国和中国报道的颗粒物质。另一方面，当详细检查自噬通量时，颗粒物质不促进自噬体的形成，但抑制自噬降解。由于这些作用与棕榈酸酯（一种脂肪酸）相似，我们制备了用丙酮去除脂质成分的颗粒物质，并将其对HepG2细胞的影响与未处理的颗粒物质进行了比较。不含脂质成分的颗粒物诱导的内质网应激较小，但与未处理的颗粒物诱导的脂滴相同。这些结果表明，肝脏脂质合成不仅受到脂质摄取的刺激，还受到颗粒物质中其他成分的刺激。
Inhalation of particulate matter with a diameter less than 2.5 µm has been reported to exacerbates fatty liver disease. However, the components and mechanisms of particulate matter involved in hepatic lipid metabolism and autophagy have not been fully elucidated. We found that atmospheric particulate matter in Japan stimulated lipogenesis in hepatocytes even when its lipid component was removed. Furthermore, we demonstrated that particulate matter did not promote autophagosome formation but inhibited autophagic degradation in hepatocytes. In previous toxicity experiments, particulate matter collected from atmosphere often contained contaminants originating from filters. In this study, we exposed the powdery particulate matter with less contaminants collected using a cyclone and impactor system to HepG2 cells, human hepatocyte. This particulate matter induced lipogenesis and endoplasmic reticulum stress in HepG2 cells as well as previous reports of particulate matter in the USA and China. On the other hand, when autophagic flux were examined in detail, the particulate matter did not promote autophagosome formation, but inhibited autophagic degradation. Since these effects were similar to those of palmitate, a fatty acid, we prepared particulate matter in which lipid component was removed by acetone and compared the effects on HepG2 cells with those of untreated one. The particulate matter without lipid component induced lipid droplets as well as did the untreated one although it induced less endoplasmic reticulum stress. These results suggest that hepatic lipid synthesis is stimulated not only by the uptake of lipid but also by other components in the particulate matter.