Heat stress-induced endoplasmic reticulum stress promotes liver apoptosis in largemouth bass (Micropterus salmoides)

Heat stress (HS), an important factor that affects the physiological state of fish, is known to induce apoptosis. To investigate relationships among HS, endoplasmic-reticulum stress (ERS) and apoptosis in fish liver, 72 largemouth bass were randomly exposed to three different water temperatures (33 degrees C, 35 degrees C and 37 degrees C) for 6 h. Then, histological sections and TUNEL assays were analyzed to evaluate the physiological status of the liver. Transcriptome analysis and RT-qPCR were also performed to discover the key pathways involved. HS caused liver tissue damage, enhanced the apoptotic index and up-regulated the expressions of caspase-3, caspase-8, caspase-9 and ER stress marker genes such as grp78 and grp94. The differentially expressed genes (DEGs) under HS were mainly enhanced in 'protein processing in endoplasmic reticulum' pathway. In particular, the PERK and ATF6 pathway genes including perk, eif2a, atf4, chop, bcl-2 and atf6 were significantly up-regulated at 33 degrees C and 35 degrees C, while the IRE1 pathway genes including irel, traf2, askl, jnkl and jnk2 were significantly up-regulated with increasing temperature. These findings suggest that HS induced apoptosis and damage of largemouth bass liver were mainly mediated via ER-stress and the IRE1-signaling pathways. This study, which is the first to reveal that HS-induced ER stress triggers cellular apoptosis in largemouth bass liver, could provide a new approach to the study of HS in fish in the context of global warming.