New insights into ER stress mediated by ATF6 and IRE1-XBP1 signals in yellow catfish under hypoxia

In aquaculture, fish are often exposed to the major stressor of hypoxia. However, the mechanism of hypoxiainduced stress remains unclear. The present study aimed to investigate the physiological and molecular responses of yellow catfish (Pelteobagrus fulvidraco) to hypoxia stress and to further elucidate its stress response mechanisms. Each fish (28.14 +/- 0.75 g) in the hypoxia group was individually placed in a 1 L transparent plastic tank and transferred to a closed hypoxia environment, where the oxygen and carbon dioxide levels were adjusted to 2 % and 0.5 %, respectively. The results showed that hypoxia stress induced a stress response in yellow catfish, characterized by significant changes in lactate dehydrogenase (LD) and cortisol levels in plasma and liver, as well as increased apoptosis of brain cells and liver damage. Additionally, the HPA axis was activated, playing a crucial role in stress regulation during hypoxia exposure. And under hypoxia conditions, endoplasmic reticulum (ER) stress pathways were activated in yellow catfish liver, specifically showing significant upregulation of the activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1 (IRE1)-X-box binding protein 1 (XBP1) signals, while the activated transcription factor 4 (ATF4) pathway remained inactive. The expression levels of atf6, ire1 and xbp1 genes, as well as ATF6, IRE1 and XBP1 proteins in the ATF6 and IRE1-XBP1 pathways, were significantly elevated. However, there was no significant differences in the expression levels of protein kinase Rlike ER kinase (perk), eukaryotic translation initiation factor 2 alpha (eif2 alpha) and atf4 key genes, as well as PERK, EIF2 alpha and ATF4 proteins in the PERK-ATF4 pathway. It is concluded for the first time that hypoxia significantly activates ER stress through the ATF6 and IRE1-XBP1 signaling pathways, but not the PERK-ATF4 pathway in yellow catfish. These findings not only provide new insights into the stress response mechanisms of fish but also offer the accurate molecular target of hypoxia-induced stress for aquaculture management.