PEG35 as a Preconditioning Agent against Hypoxia/Reoxygenation Injury

International Journal of Molecular Sciences

Ivo F. Machado¹  Anabela P. Rolo²  Carlos M. Palmeira²  Rui Teixeira da Silva²  João S. Teodoro²  Joan Roselló-Catafau³  Arnau Panisello-Roselló³ 

[1] Center for Neurosciences and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal;Department of Life Sciences, University of Coimbra, 3000-456 Coimbra, Portugal;Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, Spain;

关键词: polyethylene glycol 35;    hypoxia/reoxygenation injury;    mitochondria;    autophagy;   

DOI  :  10.3390/ijms23031156

来源: DOAJ

【 摘 要 】

Pharmacological conditioning is a protective strategy against ischemia/reperfusion injury, which occurs during liver resection and transplantation. Polyethylene glycols have shown multiple benefits in cell and organ preservation, including antioxidant capacity, edema prevention and membrane stabilization. Recently, polyethylene glycol 35 kDa (PEG35) preconditioning resulted in decreased hepatic injury and protected the mitochondria in a rat model of cold ischemia. Thus, the study aimed to decipher the mechanisms underlying PEG35 preconditioning-induced protection against ischemia/reperfusion injury. A hypoxia/reoxygenation model using HepG2 cells was established to evaluate the effects of PEG35 preconditioning. Several parameters were assessed, including cell viability, mitochondrial membrane potential, ROS production, ATP levels, protein content and gene expression to investigate autophagy, mitochondrial biogenesis and dynamics. PEG35 preconditioning preserved the mitochondrial function by decreasing the excessive production of ROS and subsequent ATP depletion, as well as by recovering the membrane potential. Furthermore, PEG35 increased levels of autophagy-related proteins and the expression of genes involved in mitochondrial biogenesis and fusion. In conclusion, PEG35 preconditioning effectively ameliorates hepatic hypoxia/reoxygenation injury through the enhancement of autophagy and mitochondrial quality control. Therefore, PEG35 could be useful as a potential pharmacological tool for attenuating hepatic ischemia/reperfusion injury in clinical practice.

【 授权许可】

Unknown