再灌注损伤
粒体自噬
缺血
医学
药理学
肝移植
品脱1
肝细胞
帕金
移植
内科学
生物
细胞凋亡
自噬
生物化学
体外
疾病
帕金森病
作者
Yu Zhang,Ziyi Wang,Jia Chen,Wenjie Yu,Xiangdong Li,Nan Xia,Huiling Nie,Pascalia Wikana Likalamu,Minhao Chen,Yushan Ni,Song Han,Liyong Pu
标识
DOI:10.1016/j.jcmgh.2023.09.004
摘要
Hepatic ischemia-reperfusion injury is a significant complication of partial hepatic resection and liver transplantation, impacting the prognosis of patients undergoing liver surgery. The protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily synthesized by hepatocytes and has been implicated in myocardial ischemic diseases. However, the role of PCSK9 in hepatic ischemia-reperfusion injury remains unclear. This study aims to investigate the role and mechanism of PCSK9 in hepatic ischemia-reperfusion injury.We first examined the expression of PCSK9 in mouse warm ischemia-reperfusion models and AML12 cells subjected to hypoxia/reoxygenation. Subsequently, we explored the impact of PCSK9 on liver ischemia-reperfusion injury by assessing mitochondrial damage and the resulting inflammatory response.Our findings reveal that PCSK9 is up-regulated in response to ischemia-reperfusion injury and exacerbates hepatic ischemia-reperfusion injury. Blocking PCSK9 can alleviate hepatocyte mitochondrial damage and the consequent inflammatory response mediated by ischemia-reperfusion. Mechanistically, this protective effect is dependent on mitophagy.Inhibiting PCSK9 in hepatocytes attenuates the inflammatory responses triggered by reactive oxygen species and mitochondrial DNA by promoting PINK1-Parkin-mediated mitophagy. This, in turn, ameliorates hepatic ischemia-reperfusion injury.
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