Regulation of antioxidant functions during salinity stress
Aldehydes are toxic carbonyl compounds which can be created in the body as a byproduct of lipid peroxidation and a variety of other metabolic processes (Laskar & Younus, 2019), and are converted into non-harmful compounds by ALDH. In one study, lipid peroxidation increased significantly by 48h after initially decreasing following acute transfer to high salinity in the croaker fish Pseudosciaena crocea , suggesting that antioxidant pools were reduced and that the system was overwhelmed over time (Zeng, Ai, Wang, Zhang, & Wu, 2017). Other regulated cellular functions align well with known responses to salinity stress including additional solute transporters in network 2, oxidative phosphorylation in network 4, and DNA protection in network 5. These findings agree with the notion that oxidative stress is a secondary, non-specific consequence of osmotic and other environmental stresses, resulting from upregulation of oxidative metabolism and the associated increase in oxygen radical leakage (Kültz, 2020). ALDH3 is up-regulated in response to hydrocarbon exposure in mice (Lindros et al., 1998), and found to be highly responsive to phenylurea herbicides in teleost fish (Marlatt & Martyniuk, 2017). The specific isoform of UGT significantly up-regulated in this data set, UGT2C1-X2 (FC=4.03, p=.030) , was found to be transcriptionally up-regulated in Cynoglossus semilaevisflatfish in response to the environmental pollutant Perfluorooctane sulfonate (Zhang, Sun, Chen, Zhang, & Cai, 2020).
Many of the other proteins found in network 3 have detoxification/ antioxidant functions, including the aldo-keto reductases and the significantly regulated quinoid dihydropteridine reductase (QDPR) (FC=9.84, p=.039). QDPR was shown to induce production of major antioxidant enzymes including glutathione peroxidase 3 and superoxide dismutase 1 in cell culture (Gu et al., 2017). Like ALDH and DHRS (significant but not found in STRING network 3), aldo/keto reductases are another system for metabolizing toxic aldehydes (Laskar & Younus, 2019) but they were non-significantly down-regulated in BW acclimated tilapia. Therefore, our data suggest that ALDH3 and QDPR are more important for kidney function in BW acclimated tilapia than the aldo/keto reductases.
Many of the proteins in STRING network 1 are also involved in protecting against oxidative stress, including thioredoxin related proteins and several glutathione S-transferase (GST) isoforms. Evidence from rats exposed to polycyclic hydrocarbons indicates co-induction of ALDH3 along with GST in liver tissue, which points to common enhancers or transcription factors (Lindros et al., 1998). Three different GST isoforms are connected in network 1 to another highly regulated protein, elongation factor 1-delta (FC=4.48, p=.0025). EF 1-delta was found to be regulated in several studies of fish exposed to pollutants (Jeffries, Brander, Britton, Fangue, & Connon, 2015; Williams, Gensberg, Minchin, & Chipman, 2003) and putative disease agents (Lü et al., 2014), as well as hypo-osmotic stress in shrimp (Liu et al., 2016).