Activation of ALDH2 with Low Concentration of Ethanol Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetes Rat Model.
The aim of this paper is to observe the change of mitochondrial aldehyde dehydrogenase 2 (ALDH2) when diabetes mellitus (DM) rat heart was subjected to ischemia/reperfusion (I/R) intervention and analyze its underlying mechanisms. DM rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vitro and pretreated with ALDH2 activator ethanol (EtOH); cardiomyocyte in high glucose (HG) condition was pretreated with ALDH2 activator Alda-1. In control I/R group, myocardial tissue structure collapse appeared. Compared with control I/R group, left ventricular parameters, SOD activity, the level of Bcl-2/Bax mRNA, ALDH2 mRNA, and protein expressions were decreased and LDH and MDA contents were increased, meanwhile the aggravation of myocardial structure injury in DM I/R group. When DM I/R rats were pretreated with EtOH, left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 expression were increased; LDH, MDA, and myocardial structure injury were attenuated. Compared with DM + EtOH I/R group, cyanamide (ALDH2 nonspecific blocker), atractyloside (mitoPTP opener), and wortmannin (PI3K inhibitor) groups all decreased left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 and increased LDH, MDA, and myocardial injury. When cardiomyocyte was under HG condition, CCK-8 activity and ALDH2 protein expression were decreased. Alda-1 increased CCK-8 and ALDH2. Our findings suggested enhanced ALDH2 expression in diabetic I/R rats played the cardioprotective role, maybe through activating PI3K and inhibiting mitoPTP opening.
Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
Pin-Fang
PF
Kang
Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu 233030, China.
Wen-Juan
WJ
Wu
Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
Yang
Y
Tang
Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
Ling
L
Xuan
Department of Physiology, Bengbu Medical College, Bengbu 233030, China.
Su-Dong
SD
Guan
Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
Bi
B
Tang
Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
Heng
H
Zhang
Department of Physiology, Bengbu Medical College, Bengbu 233030, China.
Qin
0000-0002-7599-4295
Q
Gao
Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
Hong-Ju
0000-0003-0028-6451
HJ
Wang
D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D006352:Heart Ventricles / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010477:Perfusion; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D000431:Ethanol; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat