首页|RIP1/3-dependent programmed necrosis induces intestinal injury in septic rats

RIP1/3-dependent programmed necrosis induces intestinal injury in septic rats

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The regulation of various types of cell death may help to restore the normal physiological function of cells and play a protective role in sepsis.In the current study,we explore the role of programmed cell necrosis in sepsis and the underlying mechanisms.The septic rat model is established by Cecal-ligation and perforation(CLP),and the in vitro model is established by LPS in IEC-6 cells.Our results demonstrate that receptor-interacting protein 1(RIP1)is significantly upregulated in the ileum of septic rats and LPS-treated IEC-6 cells at both the mRNA and protein levels.Nec-1,an inhibitor of RIP1,reduces the protein levels of RIP1,p-RIP3,and phosphorylated mixed-lineage kinase domain-like(MLKL)(serine 358)and relieves intestinal injury in CLP-induced septic rats with decreased IL-6 and TNF-α levels.The in vitro experiments further reveal that LPS induces the colocalization of RIP1 and RIP3,resulting in the phosphorylation and translocation of MLKL to the plasma membrane in IEC-6 cells.LPS also facilitates ROS production in IEC-6 cells,but this effect is further reversed by Nec-1,si-RIP1 and si-RIP3.Furthermore,LPS-induced necrosis in IEC-6 cells is counteracted by NAC.Thus,we conclude that RIP1/RIP3-dependent programmed cell necrosis participates in intestinal injury in sepsis and may be associated with RIP1/RIP3-mediated ROS.

RIP1RIP3MLKLROSprogrammed cell necrosissepsis

Siting Ye、Xinxin Qi、Yuxiao Liu、Liangming Zhuang、Zhongmin Gu

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Department of Intensive Care Unit,Fuzhou Second Hospital of Xiamen University,School of Medicine,Xiamen University,Fuzhou Second Hospital,Fuzhou 350007,China

Natural Science Foundation of Fujian Province Supported ProjectFujian Provincial Clinical Medical Research Center for First Aid and Rehabilitation in Orthopaedic Trauma,Fujian,China

2021J0113182020Y2014

2024

10.3724/abbs.2023248

生物化学与生物物理学报(英文版)
中国科学院上海生物化学研究所

生物化学与生物物理学报(英文版)

CSTPCD
影响因子：0.772
ISSN：1672-9145
年,卷(期)：2024.56(1)
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