Format

Send to

Choose Destination
Transpl Int. 2016 Jan;29(1):98-107. doi: 10.1111/tri.12675. Epub 2015 Sep 25.

Decreased expression of mitochondrial aldehyde dehydrogenase-2 induces liver injury via activation of the mitogen-activated protein kinase pathway.

Author information

1
Wuhan University, Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan Hubei, China.
2
Jianghan District Center for Disease Control and Prevention, Wuhan Hubei, China.
3
The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha, China.
4
Massachusetts General Hospital, Department of Urology, Harvard Medical School, Boston, MA, USA.

Abstract

The aim of this study was to determine the role of ALDH2 in the injury of liver from brain-dead donors. Using brain-dead rabbit model and hypoxia model, levels of ALDH2 and apoptosis in tissues and cell lines were determined by Western blot, flow cytometry (FCM), and transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) assays. After the expression of ALDH2 during hypoxia had been inhibited or activated, the accumulations of 4-hydroxynonenal (4-HNE) and molecules involved in mitogen-activated protein kinase (MAPK) signaling pathway were analyzed using ELISA kit and Western blot. The low expression of phosphorylated ALDH2 in liver was time-dependent in the brain-dead rabbit model. Immunohistochemistry showed ALDH2 was primarily located in endothelial, and the rates of cell apoptosis in the donation after brain-death (DBD) rabbit groups significantly increased with time. Following the treatment of inhibitor of ALDH2, daidzein, in combination with hypoxia for 8 h, the apoptosis rate and the levels of 4-HNE, P-JNK, and cleaved caspase-3 significantly increased in contrast to that in hypoxic HUVECs; however, they all decreased after treatment with Alda-1 and hypoxia compared with that in hypoxic HUVECs (P < 0.05). Instead, the levels of P-P38, P-ERK, P-JNK, and cleaved caspase-3 decreased and the ratio of bcl-2/bax increased with ad-ALDH2 (10(6) pfu/ml) in combination with hypoxia for 8 h, which significantly alleviated in contrast to that in hypoxic HUVECs. We found low expression of ALDH2 and high rates of apoptosis in the livers of brain-dead donor rabbits. Furthermore, decreased ALDH2 led to apoptosis in HUVECs through MAPK pathway.

KEYWORDS:

apoptosis; brain death; mitochondrial aldehyde dehydrogenase 2; mitogen-activated protein kinase pathway

PMID:
26404764
DOI:
10.1111/tri.12675
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center