Oncotarget

Research Papers:

Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury

Baoshan Liu, Jiali Wang, Minghua Li, Qiuhuan Yuan, Mengyang Xue, Feng Xu and Yuguo Chen _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:19413-19426. https://doi.org/10.18632/oncotarget.14297

Metrics: PDF 1819 views  |   HTML 2662 views  |   ?  


Abstract

Baoshan Liu1,2,3,4,*, Jiali Wang1,2,3,4,*, Minghua Li1,2,3,4, Qiuhuan Yuan1,2,3,4, Mengyang Xue1,2,3,4, Feng Xu1,2,3,4, Yuguo Chen1,2,3,4

1Department of Emergency, Qilu Hospital, Shandong University, Jinan, China

2Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China

3Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China

4Key Laboratory of Cardiovascular Remodeling & Function Research, Chinese Ministry of Education & Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China

*These authors have contributed equally to this work

Correspondence to:

Yuguo Chen, email: [email protected]

Feng Xu, email: [email protected]

Keywords: myocardial ischemia/reperfusion, hyperglycemia, ALDH2, O-GlcNAcylation

Received: May 20, 2016    Accepted: November 30, 2016    Published: December 27, 2016

ABSTRACT

Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). ALDH2 O-GlcNAc modification was increased whereas its activity was decreased in AHG+I/R and DM+I/R rats. High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). Accordingly, ALDH2 activity was decreased by 18.1% in Con+PUGNAc group whereas it was increased by 17.9% in Con+DON group. Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 14297