School of Public Health, Bengbu Medical College, Bengbu, People's Republic of China.
School of Life Science, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, People's Republic of China.
Ecotoxicol Environ Saf. 2022 Dec 15;248:114289. doi: 10.1016/j.ecoenv.2022.114289. Epub 2022 Nov 12.
Graphene oxide (GO) exposure may cause damage to C. elegans. However, the role of autophagy and its interactive effect with oxidative response in GO toxicity still remain largely unclear. In the present study, we investigated the protective role of autophagy against GO and its association with oxidative response using C. elegans as an in vivo system. Results indicated that GO exposure induced autophagy in a dose dependent manner in C. elegans. Autophagy inhibitor 3-methyladenine (3-MA) and silencing autophagy genes lgg-1, bec-1 and unc-51 exacerbated the toxicity of GO whereas autophagy activator rapamycin alleviated it. In addition, the antioxidant N-Acetyl-L-cysteine (NAC) effectively suppressed the toxicity of GO with increased resistance to oxidative stress. Worms with RNAi-induced antioxidative genes sod-1, sod-2, sod-3 and sod-4 knockdown were more sensitive to GO. 3-MA increased the expression of superoxide dismutase SOD-3 under GO exposure conditions and exacerbated the toxicity of GO under the anti-oxidation inaction condition by sod-3 RNAi. In contrast, NAC reduced autophagy levels in GO exposed nematodes and increased tolerance to GO in autophagy-defective worms. These results suggested that autophagy and antioxidative response provide complementary protection against GO in C. elegans.
氧化石墨烯（GO）暴露可能会对秀丽隐杆线虫造成损害。然而，自噬的作用及其与氧化应激的相互作用在 GO 毒性中的作用在很大程度上仍不清楚。在本研究中，我们使用秀丽隐杆线虫作为体内系统，研究了自噬对 GO 的保护作用及其与氧化应激的关系。结果表明，GO 暴露以剂量依赖的方式诱导秀丽隐杆线虫中的自噬。自噬抑制剂 3-甲基腺嘌呤（3-MA）和沉默自噬基因 lgg-1、bec-1 和 unc-51 加剧了 GO 的毒性，而自噬激活剂雷帕霉素则减轻了毒性。此外，抗氧化剂 N-乙酰-L-半胱氨酸（NAC）通过增加对氧化应激的抵抗力，有效抑制了 GO 的毒性。具有 RNAi 诱导抗氧化基因 sod-1、sod-2、sod-3 和 sod-4 敲低的线虫对 GO 更敏感。在 GO 暴露条件下，3-MA 增加了超氧化物歧化酶 SOD-3 的表达，并通过 sod-3 RNAi 在抗氧化作用丧失的条件下加剧了 GO 的毒性。相比之下，NAC 降低了 GO 暴露线虫中的自噬水平，并增加了自噬缺陷线虫对 GO 的耐受性。这些结果表明，自噬和抗氧化应激反应为秀丽隐杆线虫中的 GO 提供了互补的保护。
