自噬
肺
肺移植
移植
PI3K/AKT/mTOR通路
冷库
缺血
药理学
医学
内科学
灌注
化学
生物
生物化学
信号转导
细胞凋亡
园艺
作者
Hongyuan Lin,Shaohua Dai,Weicheng Liu,Xiaoying Lin,Bentong Yu,Shi-Biao Chen,Sheng Liu,Hua Lu,Jian Tang
出处
期刊:Life Sciences
[Elsevier]
日期:2021-03-01
卷期号:268: 118820-118820
被引量:4
标识
DOI:10.1016/j.lfs.2020.118820
摘要
Ischemia-reperfusion (I/R) injury causes present challenges in the field of graft transplantation which is also a major contributor to early graft dysfunction or failure after organ transplantation. The study focuses on the effects of prolonged cold-ischemia (CI) on the autophagic activity in the graft lung in a rat orthotopic lung transplantation model. Donor lungs were preserved under CI conditions for different periods. An orthotopic lung transplantation model was developed, and the lung tissues from donor lungs subjected to CI preservation and reperfusion were harvested. We evaluated the effects of different CI periods on autophagy, reactive oxygen species (ROS) and glucose consumption. Additionally, the mechanism by which prolonged CI affected autophagy was investigated through determination of the molecules related to the mTOR pathway after treatment with 3-Methyladenine (3-MA), rapamycin and an adenosine triphosphate (ATP) synthase inhibitor oligomycin (OM). Prolonged CI led to increased activities of key glycolytic enzymes, glucose consumption and lactic acid production. Autophagy, ROS and glucose consumption were induced in the graft lung after I/R, which reached peak levels after 6 h and was gradually decreased. Most importantly, the perfusion treatment of 3-MA or OM decreased ROS level and autophagy, but increased the extent of mTOR phosphorylation, while the perfusion treatment of rapamycin induced ROS and autophagy. Taken together, autophagy mediated by a prolonged CI preservation affects the glucose consumption and ROS production in the graft lung via the mTOR signaling pathway.
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