title: Autophagy lessens ischemic liver injury by reducing oxidative damage.
abstract: BACKGROUND
  Hepatic ischemia/reperfusion is a multi-factorial process which causes liver injury. It is reported that ischemia alone is sufficient to induce liver injury. Nutrient deprivation is a crucial factor impacting ischemic injury of the liver. Therefore, we explored the role of autophagy in ischemia through using hepatic ischemia rat model in vivo and nutrient-free model in vitro.
  
  
  RESULTS
  We found that both ischemia in vivo and nutrient deprivation in vitro activated autophagy, inhibition of which aggravated ischemia- or nutrient deficiency-induced injury. In the nutrient-free condition, autophagy inhibition enhanced liver cell necrosis but not apoptosis by promoting reactive oxygen species (ROS) accumulation, and antioxidant NAC could reverse this trend. Inhibition of autophagy also resulted in the increase of the percentage of necrotic cell but not apoptotic cell in the ischemia-treated rat livers. Further studies showed that under nutrient deprivation, autophagy inhibition promoted mitochondrial ROS generation, which further aggravated mitochondria damage. These changes formed a "vicious cycle" that accelerated the process of cell necrosis. Autophagy inhibition also increased mitochondrial oxidative stress during hepatic ischemia, and antioxidant could suppress the aggravation of ischemia-induced liver damage in the co-treatment of autophagy inhibitor.
  
  
  CONCLUSIONS
  Taken together, our results suggested that autophagy suppressed ischemic liver injury by reducing ROS-induced necrosis. This finding will contribute to the development of the therapeutic strategy about the pre-treatment of liver surgery.
authors.affiliation: Medical Sciences Research Center, Renji hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.|Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: Medical Sciences Research Center, Renji hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.|Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Xuqin
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Radiation Oncology, Affiliated Tumor Hospital of GuangXi Medical University, Guangxi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Han
authors.affiliation: Medical Sciences Research Center, Renji hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Medical Sciences Research Center, Renji hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Cai
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Jianrui
authors.initials: J
authors.lastname: Song
authors.affiliation: Medical Sciences Research Center, Renji hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.|Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei