PMID- 20705694
OWN - NLM
STAT- MEDLINE
DCOM- 20120106
LR  - 20220712
IS  - 1522-9645 (Electronic)
IS  - 0195-668X (Print)
IS  - 0195-668X (Linking)
VI  - 32
IP  - 8
DP  - 2011 Apr
TI  - Aldehyde dehydrogenase 2 (ALDH2) rescues myocardial ischaemia/reperfusion injury: 
      role of autophagy paradox and toxic aldehyde.
PG  - 1025-38
LID - 10.1093/eurheartj/ehq253 [doi]
AB  - AIMS: The present study was designed to examine the mechanism involved in 
      mitochondrial aldehyde dehydrogenase (ALDH2)-induced cardioprotection against 
      ischaemia/reperfusion (I/R) injury with a focus on autophagy. METHODS: Wild-type 
      (WT), ALDH2 overexpression, and knockout (KO) mice (n = 4-6 for each index 
      measured) were subjected to I/R, and myocardial function was assessed using 
      echocardiographic, Langendroff, and edge-detection systems. Western blotting was 
      used to evaluate AMP-dependent protein kinase (AMPK), Akt, autophagy, and the 
      AMPK/Akt upstream signalling LKB1 and PTEN. RESULTS: ALDH2 overexpression and KO 
      significantly attenuated and accentuated, respectively, infarct size, factional 
      shortening, and recovery of post-ischaemic left ventricular function following 
      I/R as well as hypoxia/reoxygenation-induced cardiomyocyte contractile 
      dysfunction. Autophagy was induced during ischaemia and remained elevated during 
      reperfusion. ALDH2 significantly promoted autophagy during ischaemia, which was 
      accompanied by AMPK activation and mammalian target of rapamycin (mTOR) 
      inhibition. On the contrary, ALDH2 overtly inhibited autophagy during reperfusion 
      accompanied by the activation of Akt and mTOR. Inhibition and induction of 
      autophagy mitigated ALDH2-induced protection against cell death in hypoxia and 
      reoxygenation, respectively. In addition, levels of the endogenous toxic aldehyde 
      4-hydroxy-2-nonenal (4-HNE) were elevated by ischaemia and reperfusion, which was 
      abrogated by ALDH2. Furthermore, ALDH2 ablated 4-HNE-induced cardiomyocyte 
      dysfunction and protein damage, whereas 4-HNE directly decreased pan and 
      phosphorylated LKB1 and PTEN expression. CONCLUSION: Our data suggest a 
      myocardial protective effect of ALDH2 against I/R injury possibly through 
      detoxification of toxic aldehyde and a differential regulation of autophagy 
      through AMPK- and Akt-mTOR signalling during ischaemia and reperfusion, 
      respectively.
FAU - Ma, Heng
AU  - Ma H
AD  - Department of Physiology, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, 710032, China.
FAU - Guo, Rui
AU  - Guo R
FAU - Yu, Lu
AU  - Yu L
FAU - Zhang, Yingmei
AU  - Zhang Y
FAU - Ren, Jun
AU  - Ren J
LA  - eng
GR  - 1R01 AA013412/AA/NIAAA NIH HHS/United States
GR  - P20RR016474/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100812
PL  - England
TA  - Eur Heart J
JT  - European heart journal
JID - 8006263
RN  - 0 (Aldehydes)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - EC 1.2.1.3 (ALDH2 protein, mouse)
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase)
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase, Mitochondrial)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
SB  - IM
MH  - Aldehyde Dehydrogenase/metabolism/*physiology
MH  - Aldehyde Dehydrogenase, Mitochondrial
MH  - Aldehydes/metabolism/pharmacology
MH  - Animals
MH  - Autophagy/physiology
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria, Heart/enzymology
MH  - Myocardial Contraction/physiology
MH  - Myocardial Infarction/enzymology/pathology
MH  - Myocardial Reperfusion Injury/*enzymology
MH  - Myocytes, Cardiac/enzymology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3076664
EDAT- 2010/08/14 06:00
MHDA- 2012/01/10 06:00
PMCR- 2012/04/01
CRDT- 2010/08/14 06:00
PHST- 2010/08/14 06:00 [entrez]
PHST- 2010/08/14 06:00 [pubmed]
PHST- 2012/01/10 06:00 [medline]
PHST- 2012/04/01 00:00 [pmc-release]
AID - ehq253 [pii]
AID - 10.1093/eurheartj/ehq253 [doi]
PST - ppublish
SO  - Eur Heart J. 2011 Apr;32(8):1025-38. doi: 10.1093/eurheartj/ehq253. Epub 2010 Aug 
      12.