Differential regulation of endoplasmic reticulum stress-induced autophagy and apoptosis in two strains of gibel carp (Carassius gibelio) exposed to acute waterborne cadmium

Abstract

Previous studies illustrated that gibel carp F strain displays better lipid mobilization and antioxidant ability and compared to the A strain. We therefore hypothesized that the F strain would exhibit superior defense to cadmium exposure. Comparative studies were conducted between A and F strains using plasma stress biomarkers, histological observations, and analysis of hepatic molecular events to examine exposure to waterborne Cd (11.9 mg L^-1) for 48 h and 96 h. Waterborne Cd exposure stimulated stress response and hepatic metallothionein mRNA induction in both gibel carp strains confirming exposure. Antioxidant responses were stimulated to counteract Cd toxicity, suggested by the upregulation of mRNA levels of genes associated with nuclear factor erythroid 2-related factor 2 (nrf2) signaling. Cd exposure induced endoplasmic reticulum (ER) stress, meanwhile, branches of genes in unfolded protein response (UPR) were activated. Slight time-dependent effects were implied by greater ER stress, UPR, and apoptosis signals with the duration of Cd exposure. Genotype-specific effects were identified, revealing that the F strain showed greater stress at 96 h exposure and higher antioxidant response compared to the A strain, as indicated by the mRNA levels of genes in nrf2 signaling. ER stress and UPR were also stronger in the F strain after Cd exposure. In contrast, the A strain showed higher autophagy and apoptosis response compared to the F strain. Collectively, combined autophagy and apoptosis were triggered under ER stress, which might serve as defense strategies in both gibel carp strains. The F strain showed greater antioxidant detoxification response and UPR to mitigate Cd toxicity, whereas excessive ER stress contributed to higher autophagy and apoptosis in the A strain. The present study uncovered the differential regulation and defense strategies in fish strains exposed to metal exposure.

Keywords: Antioxidant response; ER stress; Strain; Waterborne cadmium.