Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis  被引量:1

在线阅读下载全文

作  者:Peng-Yue Zhao Ren-Qi Yao Li-Yu Zheng Yao Wu Yu-Xuan Li Ning Dong Jing-Yan Li Xiao-Hui Du Yong-Ming Yao 

机构地区:[1]Translational Medicine Research Center,Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital,Beijing 100853,China [2]Department of General Surgery,First Medical Center of the Chinese PLA General Hospital,Beijing 100853,China [3]Department of Burn Surgery,The First Affiliated Hospital of Naval Medical University,Shanghai 200433,China [4]Department of Emergency,The Second Hospital of Hebei Medical University,Shijiazhuang 050000,China

出  处:《Burns & Trauma》2023年第1期72-90,共19页烧伤与创伤(英文)

基  金:supported by grants from the National Natural Sciences Foundation of China(Nos.81730057,82130062,81801935);Key Project of Military Medical Innovation Program of Chinese PLA(Nos.18CXZ025,18CXZ026);Provincial Key Project of Medical Science Research of Hebei(20210013).

摘  要:Background:Ribophagy is a selective autophagic process that specifically degrades dysfunctional or superfluous ribosomes to maintain cellular homeostasis.Whether ribophagy can ameliorate the immunosuppression in sepsis similar to endoplasmic reticulum autophagy(ERphagy)and mitophagy remains unclear.This study was conducted to investigate the activity and regulation of ribophagy in sepsis and to further explore the potential mechanism underlying the involvement of ribophagy in T-lymphocyte apoptosis.Methods:The activity and regulation of nuclear fragile X mental retardation-interacting protein 1(NUFIP1)-mediated ribophagy in T lymphocytes during sepsis were first investigated by western blotting,laser confocal microscopy and transmission electron microscopy.Then,we constructed lentivirally transfected cells and gene-defective mouse models to observe the impact of NUFIP1 deletion on T-lymphocyte apoptosis and finally explored the signaling pathway associated with T-cell mediated immune response following septic challenge.Results:Both cecal ligation and perforation-induced sepsis and lipopolysaccharide stimulation significantly induced the occurrence of ribophagy,which peaked at 24 h.When NUFIP1 was knocked down,T-lymphocyte apoptosis was noticeably increased.Conversely,the overexpression of NUFIP1 exerted a significant protective impact on T-lymphocyte apoptosis.Consistently,the apoptosis and immunosuppression of T lymphocytes and 1-week mortality rate in NUFIP1 gene-deficient mice were significantly increased compared with those in wild-type mice.In addition,the protective effect of NUFIP1-mediated ribophagy on T lymphocytes was identified to be closely related to the endoplasmic reticulum stress apoptosis pathway,and PERK-ATF4-CHOP signaling was obviously involved in downregulating T-lymphocyte apoptosis in the setting of sepsis.Conclusions:NUFIP1-mediated ribophagy can be significantly activated to alleviate T lymphocyte apoptosis through the PERK-ATF4-CHOP pathway in the context of sepsis.Thus,targeting NUFIP1-

关 键 词:NUFIP1 Ribophagy SEPSIS APOPTOSIS IMMUNOSUPPRESSION Autophagy MITOPHAGY LYMPHOCYTE LIPOPOLYSACCHARIDE 

分 类 号:R631[医药卫生—外科学]

 

参考文献:

正在载入数据...

 

二级参考文献:

正在载入数据...

 

耦合文献:

正在载入数据...

 

引证文献:

正在载入数据...

 

二级引证文献:

正在载入数据...

 

同被引文献:

正在载入数据...

 

相关期刊文献:

正在载入数据...

相关的主题
相关的作者对象
相关的机构对象