Transcriptional profile of genes involved in oxidative stress and antioxidant defense in PC12 cells following treatment with cerium oxide nanoparticles

摘要

Background Thanks to their impressive catalytic properties, cerium oxide nanoparticles (nanoceria) are able to mimic the activity of superoxide dismutase and of catalase, therefore acting as reactive oxygen species (ROS) scavengers in many biological contexts, for instance offering neuroprotection and reduction of apoptosis rate in many types of cells exposed to oxidative stress (stem cells, endothelial cells, epithelial cells, osteoblasts, etc.). Methods We report on the investigation at gene level, through quantitative real time RT-PCR, of the effects of cerium oxide nanoparticles on ROS mechanisms in neuron-like PC12 cells. After three days of treatment, transcription of 84 genes involved in antioxidant defense, in ROS metabolism, and coding oxygen transporters is evaluated, and its relevance to central nervous system degenerative diseases is considered. Results Experimental evidences reveal intriguing differences in transcriptional profiles of cells treated with cerium oxide nanoparticles with respect to the controls: nanoceria acts as strong exogenous ROS scavenger, modulating transcription of genes involved in natural cell defenses, down-regulating genes involved in inflammatory processes, and up-regulating some genes involved in neuroprotection. Conclusions Our findings are extremely promising for future biomedical applications of cerium oxide nanoparticles, further supporting their possible exploitation in the treatment of neurodegenerative diseases. General significance This work represents the first documented step to the comprehension of mechanisms underlying the anti-oxidant action of cerium oxide nanoparticles. Our findings allow for a better comprehension of the phenomena of ROS scavenging and neuroprotection at a gene level, suggesting future therapeutic approaches even at a pre-clinical level.