The effects of autophagy on vascular endothelial cells induced by airborne PM2.5

The purpose of this study was to examine the direct toxicity of PM2.5 collected from Beijing on human umbilical vein endothelial cells(HUVEC). A Cell Counting Kit 8(CCK8) assay demonstrated that PM2.5 exposure decreased the proliferation of HUVECs in a dosedependent manner. We also found that PM2.5 exposure induced autophagy in HUVECs, as evidenced by:(1) an increased number of double-membrane vesicles;(2) enhanced conversion and punctuation of the microtubule-associated protein light chain 3(LC3); and(3) decreased levels of the selective autophagy substrate p62 in a time-dependent manner.Furthermore, promoting autophagy in PM2.5-exposed HUVECs with rapamycin increased the cell survival rate, whereas inhibiting autophagy via 3-methyladenine significantly decreased cell survival. These results demonstrate that PM2.5 exposure can induce cytotoxicity and autophagy in HUVECs and that autophagy play a protective role against PM2.5-induced cytotoxicity. The findings of the present study imply a direct toxic effect of PM2.5 on HUVECs and provide novel insight into the mechanism of cardiovascular diseases caused by PM2.5 exposure.     

Reproductive toxicity and underlying mechanisms of di(2-ethylhexyl) phthalate in nematode Caenorhabditis elegans

DEHP (di(2-ethylhexyl) phthalate) is an endocrine disruptor commonly found in plastic products that has been associated with reproduction alterations, but the effect of DEHP on toxicity is still widely unknown. Using DEHP concentrations of 10, 1, and 0.1 mg/L, we showed that DEHP reduced the reproductive capacity of Caenorhabditis elegans after 72 hr. of exposure. DEHP exposure reduced the reproductive capacity in terms of decreased brood sizes, egg hatchability (0.1, 1 and 10 mg/L), and egg-laying rate (1 and 10 mg/L), and increased numbers of fertilized eggs in the uterus (1 and 10 mg/L). DEHP also caused damage to gonad development. DEHP decreased the total number of germline cells, and decreased the relative area of the gonad arm of all exposure groups, with worms in the 1 mg/L DEHP exposure group having the minimum gonad arm area. Additionally, DEHP caused a significant concentration‐dependent increase in the expression of unc-86. Autophagy and ROS contributed to the enhancement of DEHP toxicity in reducing reproductive capacity, and glutathione peroxidase and superoxide dismutase were activated as the antioxidant defense in this study. Hence, we found that DEHP has a dual effect on nematodes. Higher concentration (10 mg/L) DEHP can inhibit the expression of autophagy genes (atg-18, atg-7, bec-1, lgg-1 and unc-51), and lower concentrations (0.1 and 1 mg/L) can promote the expression of autophagy genes. Our data highlight the potential environmental risk of DEHP in inducing reproductive toxicity toward the gonad development and reproductive capacity of environmental organisms.     

大气中PM2.5污染现状、健康效应及其致炎症机制研究进展

空气细颗粒物(PM_(2.5))污染已成为影响人体健康的重要因素,其健康效应及致炎症机制已经受到人们的广泛关注。简述了PM_(2.5)国内外污染现状,从PM_(2.5)的质量浓度和组成成分2个方面系统地阐述了其对人体健康的危害,并重点从介导信号通路和介导细胞自噬2个方面对PM_(2.5)导致机体炎症反应的毒性机制进行了总结和讨论,为后续研究和控制PM_(2.5)对机体健康的危害提供科学参考。     

Cytotoxicity and autophagy induction by graphene quantum dots with different functional groups

Graphene quantum dots(GQDs) possess great potential in various applications due to their superior physicochemical properties and wide array of available surface modifications.However, the toxicity of GQDs has not been systematically assessed, thus hindered their further development; especially, the risk of surface modifications of GQDs is largely unknown. In this study, we employed a lung carcinoma A549 cells as the model to investigate the cytotoxicity and autophagy induction of three types GQDs, including cGQDs(COOH-GQDs), hGQDs(OH-GQDs), and aGQDs(NH_2-GQDs). The results showed hGQDs was the most toxic, as significant cell death was induced at the concentration of 100 μg/mL,determining by WST-1 assay as well as Annexin-V-FITC/PI apoptosis analysis, whereas cGQDs and aGQDs were non-cytotoxic within the measured concentration. Autophagy detection was performed by TEM examination, LC3 fluorescence tracking, and Westernblot. Both aGQDs and hGQDs induced cellular autophagy to various degrees except for cGQDs. Further analysis on autophagy pathways indicated all GQDs significantly activated p-p38 MAPK; p-ERK1/2 was inhibited by aGQDs and hGQDs but activated by c GQDs. p-JNK was inhibited by aGQDs and c GQDs, while activated by hGQDs. Simultaneously, Akt was activated by hGQDs but inhibited by aGQDs. Inhibition of autophagy by 3-MA significantly increased the cytotoxicity of GQDs, suggesting that autophagy played a protective role against the toxicity of GQDs. In conclusion, c GQDs showed excellent biocompatibility and may be considered for biological applications. Autophagy induction may be included in the health risk assessment of GQDs as it reflects the stress status which may eventually lead to diseases.