Keywords: 
• graphene oxide (GO) /
• C. elegans /
• oxidative stress /
• unfolded protein response /
• UPR

Abstract: The aim of this work was to explore the underlying mechanisms of unfolded protein response (UPR) induced by graphene oxide (GO) and the association of UPR with oxidative stress in nematode C. elegans. L4 nematodes were exposed to GO for 24 hours, then reactive oxygen species (ROS), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were evaluated. The hsp-4 and hsp-6 were used as markers for endoplasmic reticulum (UPR^ER) and mitochondria (UPR^mt) unfolded protein response respectively. The antioxidant glutathione (GSH) was used to detect the association of UPR with oxidative stress in response to the toxicity of GO. The levels of ROS, LDH and MDA were significantly increased in GO exposed C. elegans at the concentration from 1 mg·L^-1 to 100 mg·L^-1. The expression of hsp-4 and hsp-6 were significantly upregulated after GO exposure, which suggested that the UPR^mt and UPR^ER were activated by GO. The antioxidant GSH could inhibit the activation of the UPR^mt and UPR^ER response. These data demonstrated that GO exposure can induce oxidative stress in the organism of C. elegans and then activate the UPR^mt and UPR^ER. The antioxidant GSH could suppress the UPR^mt and UPR^ER through reducing the oxidative stress.