TY - JOUR TI - Histone deacetylase 2 regulates ULK1 mediated pyroptosis during acute liver failure by the K68 acetylation site AU - Wang, Yao AU - Chen, Qian AU - Jiao, Fangzhou AU - Shi, Chunxia AU - Pei, Maohua AU - Wang, Luwen AU - Gong, Zuojiong T2 - Cell Death & Disease AB - Pyroptosis is a new necrosis pattern of hepatocyte during liver inflammation in acute liver failure (ALF). Histone deacetylase 2 (HDAC2) is associated with several pathological conditions in the liver system. The aim of this study is to investigate whether knockdown or pharmacological inhibition of HDAC2 could reduce the level of pyroptosis in ALF through ULK1-NLRP3-pyroptosis pathway. The role of HDAC2 on ULK1-NLRP3-pyroptosis pathway during ALF was detected in clinical samples. The mechanism was investigated in transfected cells or in ALF mouse model. The RNA-sequencing results revealed that ULK1 was a negative target regulatory molecule by HDAC2. During the process of pyroptosis, the HDAC2 exerted the antagonistic effect with ULK1 by the K68 acetylation site in L02 cells. Then the role of HDAC2 on ULK1-NLRP3-pyroptosis pathway in ALF mouse model was also detected. Moreover, the related molecules to ULK1-NLRP3-pyroptosis pathway were verified different expression in normal health donors and clinical ALF patients. HDAC2 in hepatocytes plays a pivotal role in an ULK1-NLRP3 pathway driven auto-amplification of pyroptosis in ALF. One of the important mechanisms is that inhibition HDAC2 to reduce pyroptosis may be by modulating the K68 lysine site of ULK1. DA - 2021/01/11/ PY - 2021 DO - 10.1038/s41419-020-03317-9 DP - www.nature.com VL - 12 IS - 1 SP - 1 EP - 17 LA - en SN - 2041-4889 UR - https://www.nature.com/articles/s41419-020-03317-9 Y2 - 2021/01/11/17:18:59 ER -