Signaling Transduction\nNetwork Elucidation of ACE\n2 Regulating <i>Apostichopus japonicus</i> Autolysis by\nUsing Integrative TMT Proteomics and Transcriptomics

This study aims to reveal the transduction\nsignaling\nnetwork that\ntriggers sea cucumber (Apostichopus japonicus) autolysis. The tandem mass tag (TMT) proteomics and transcriptomic\ntechniques were used to analyze expression differences between inhibited\nand activated sea cucumber autolysis. Flow cytometry was used to identify\napoptosis. Western blotting and RT-PCR verified the signaling pathway.\nThe results showed that the angiotensin-converting enzyme 2 (ACE 2)\nactivator (diminazene, DIZE) maintained the health of A. japonicus. The ACE 2 inhibitor (captopril, Capt)\naccelerated the autolysis. Based on the multiomics analysis, the ACE\n2 activator activated the downstream NF-κB pathway to prevent\nthe sea cucumber apoptosis. The Capt activated apoptosis initiation.\nApoptosis occurred through the regulation of TNF and PI3K-Akt signaling\npathways, which downregulate NF-κB. Akt was identified as an\nintermediate signaling protein downstream of ACE 2 that regulates\nautolysis in A. japonicus. Compared\nto A. japonicus in the ultraviolet-irradiated\nand Capt groups, the Akt inhibitor (perifosine, KRX) significantly\nreduced the expression of the PI3K-Akt and NF-κB pathways, thereby\ninhibiting the autolysis process. Additionally, DIZE attenuated ROS\nlevels, thereby inhibiting the autolysis of A. japonicus. This study provides better insight into the autolysis mechanism\nof A. japonicus.