Correlation Engine 2.0
Clear Search sequence regions

  • apoptosis (1)
  • GTP (2)
  • hypothermia (10)
  • impaired (1)
  • ischemia (10)
  • level protein (1)
  • liver (6)
  • mice (1)
  • poor prognosis (1)
  • Rab7 (4)
  • rab7 protein (2)
  • Sizes of these terms reflect their relevance to your search.

    Liver ischemia-reperfusion (IR) injury is an unavoidable pathological process in transplantation, closely related to poor prognosis. To date, there has been no clear therapeutic measure. We previously reported that mild hypothermia (MH), a widely used therapy, can exert significant protective effect against liver IR injury. Among the multiple mechanisms underlying the therapeutic effect of MH, autophagy flux drew our special attention. In this study, we evaluated the role of autophagy flux in IR injury and thereby explored the relationship between MH and autophagy flux in IR injury. We developed in vivo and in vitro models for hepatic IR injury. By autophagy flux assay with Western blotting and immunofluorescence, we found that MH restricts heavy accumulation of autophagosomes (APs) during IR injury. Activation and blocking of the autophagy flux unraveled that accumulation of APs further aggravated IR injury. Further, MH reduces APs accumulation to restore autophagy flux by regulating the fusion of APs and lysosomes. Besides, MH upregulated the level of Rab7 protein expression that was seriously impaired during IR injury. Inhibition of Rab7 expression increased apoptosis of liver cells and reduced the degree of overlap between APs and lysosomes. The results were reversed upon activation of Rab7. In conclusion, MH can alleviate liver IR injury by regulating the Rab7-mediated APs-lysosomes fusion that reduces APs accumulation. This can provide a theoretical basis for the further application of MH in related clinical diseases. Copyright © 2021 Elsevier Inc. All rights reserved.


    Anxiong Liu, Wei Wang, Zhongshan Lu, Zhongzhong Liu, Wei Zhou, Zibiao Zhong, Qifa Ye. Mild hypothermia pretreatment extenuates liver ischemia-reperfusion injury through Rab7-mediated autophagosomes-lysosomes fusion. Biochemical and biophysical research communications. 2021 Apr 23;550:15-21

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 33677131

    View Full Text