Transcriptome analysis reveals the early resistance of zebrafish larvae to oxidative stress

Oxidative stress is one of most common environmental stresses encountered by fish, especially during their fragile larval stage. More and more studies are aimed at understanding the antioxidant defense mechanism of fish larvae. Herein we characterized the early resistance of zebrafish larvae to oxidative stress and investigated the underlying transcriptional regulations using RNA-seq. We found that pre-exposure of zebrafish larvae to 2 mM H₂O₂ for 1 or 3 h significantly improved their survival under higher doses of H₂O₂ (3 mM), suggesting the antioxidant defenses of zebrafish larvae were rapidly built under pre-exposure of H₂O₂. Comparative transcriptome analysis showed that 310 (185 up and 125 down) and 512 (331 up and 181 down) differentially expressed genes were generated after 1 and 3 h of pre-exposure, respectively. KEGG enrichment analysis revealed that protein processing in endoplasmic reticulum is a highly enriched pathway; multiple genes (e.g., hsp70.1, hsp70.2, and hsp90aa1.2) encoding heat shock proteins in this pathway were sharply upregulated presumably to correct protein misfolding and maintaining the cellular normal functions during oxidative stress. More importantly, the Keap1/Nrf2 system-mediated detoxification enzyme system was significantly activated, which regulates the upregulation of target genes (e.g., gstp1, gsr, and prdx1) to scavenger reactive oxygen species, thereby defending against apoptosis. In addition, the MAPK, as a transmitter of stress signals, was activated, which may play an important role in activating antioxidant system in the early stages of oxidative stress. Altogether, these findings demonstrate that zebrafish larvae rapidly establish resistance to oxidative stress, and this involves changes in protein processing, stress signal transmission, and the activation of detoxification pathways.