Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Objective: To determine the role of ALDH2 in the injury of liver from brain-dead donors.
Methods: Using brain-dead rabbit model, the expression of ALDH2 and apoptosis rates in tissues and cell lines were detected by western blot, transferase (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL) assays and flow cytometry. After inhibiting or overexpression of ALDH2 (Ad-ALDH2) during hypoxia-ischemia, the accumulations of 4-Hydroxynonenal (4-HNE) and molecules involved in mitogen-activated protein kinase (MAPK) signaling pathway were analyzed by western blot.
Results: The low expression of phosphorylated ALDH2 in liver were time-dependent in the brain-dead groups, immunohistochemistry showed expression of ALDH2 was primarily located in endothelial cells. TUNEL demonstrated apoptosis rates in the brain-dead groups significantly increased with time. In vitro, after 8 hours' hypoxia-ischemia (HI group), the apoptosis rates of HUVECs (7.450±0.755%) were sharply increased (0.250±0.129%) (P<0.001), furthermore, the expression of 4-HNE, P-P38, P-ERK, P-JNK, cleaved caspase-3 and Bax were significantly higher when compared with normal control (P<0.05). Following the treatment of inhibitor of ALDH2, daidzin, the apoptosis rates in HUVECs (25.60±2.877%), the levels of 4-HNE, P-JNK, and cleaved caspase-3 in cells were significantly increased in contrast to HI group, but which all decreased after overexpression of ALDH2 when compared with HI group (P<0.001) .
Conclusion: We found low expression of ALDH2 and high rates of apoptosis in the livers of donor brain-dead rabbits. Furthermore, decreased ALDH2 led to apoptosis in HUVECs through MAPK pathway.
To cite this abstract in AMA style:Zhong Z, Ye S, Xiong Y, Fan X, Huang W, Ko D, Wang Y, Ye Q. Decreased Expression of Mitochondrial Aldehyde Dehydrogenase 2 Induces Liver Injury Via Activation of the MAPK Pathway in Grafts from Brain-Dead Donors [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/decreased-expression-of-mitochondrial-aldehyde-dehydrogenase-2-induces-liver-injury-via-activation-of-the-mapk-pathway-in-grafts-from-brain-dead-donors/. Accessed September 30, 2020.
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