Format

Send to

Choose Destination
Oncotarget. 2017 Aug 24;8(43):74791-74805. doi: 10.18632/oncotarget.20422. eCollection 2017 Sep 26.

Diallyl trisulfide exerts cardioprotection against myocardial ischemia-reperfusion injury in diabetic state, role of AMPK-mediated AKT/GSK-3β/HIF-1α activation.

Yu L1, Di W2, Dong X3,4, Li Z1, Xue X1, Zhang J1, Wang Q1,5, Xiao X1,6, Han J1, Yang Y7,8, Wang H1.

Author information

1
Department of Cardiovascular Surgery, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning 110016, China.
2
Department of Cardiology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
3
Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning 110016, China.
4
Department of Neurosurgery, General Hospital of Shenyang Military Area Command, Shenyang, Liaoning 110016, China.
5
Graduate School, Dalian Medical University, Dalian, Liaoning 116044, China.
6
Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
7
Faculty of Life Science, Northwest University, Xi'an, Shaanxi 710069, China.
8
Department of Biomedical Engineering, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.

Abstract

Diallyl trisulfide (DATS), the major active ingredient in garlic, has been reported to confer cardioprotective effects. However, its effect on myocardial ischemia-reperfusion (MI/R) injury in diabetic state and the underlying mechanism are still unknown. We hypothesize that DATS reduces MI/R injury in diabetic state via AMPK-mediated AKT/GSK-3β/HIF-1α activation. Streptozotocin-induced diabetic rats received MI/R surgery with or without DATS (20mg/kg) treatment in the presence or absence of Compound C (Com.C, an AMPK inhibitor, 0.25mg/kg) or LY294002 (a PI3K inhibitor, 5mg/kg). We found that DATS significantly improved heart function and reduced myocardial apoptosis. Additionally, in cultured H9c2 cells, DATS (10μM) also attenuated simulated ischemia-reperfusion injury. We found that AMPK and AKT/GSK-3β/HIF-1α signaling were down-regulated under diabetic condition, while DATS markedly increased the phosphorylation of AMPK, ACC, AKT and GSK-3β as well as HIF-1α expression in MI/R-injured myocardium. However, these protective actions were all blunted by Com.C administration. Additionally, LY294002 abolished the stimulatory effect of DATS on AKT/GSK-3β/HIF-1α signaling without affecting AMPK signaling. While 2-methoxyestradiol (a HIF-1α inhibitor) reduced HIF-1α expression without affecting AKT/GSK-3β signaling. Taken together, these data showed that DATS protected against MI/R injury in diabetic state by attenuating cellular apoptosis via AMPK-mediated AKT/GSK-3β/HIF-1α signaling. Its cardioprotective effect deserves further study.

KEYWORDS:

AKT/GSK-3β/HIF-1α signaling; AMPK; diabetes mellitus; diallyl trisulfide; myocardial ischemia-reperfusion injury

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare that they have no competing interests.

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center