PMID- 23689279
OWN - NLM
STAT- MEDLINE
DCOM- 20140131
LR  - 20220408
IS  - 1748-7838 (Electronic)
IS  - 1001-0602 (Print)
IS  - 1001-0602 (Linking)
VI  - 23
IP  - 7
DP  - 2013 Jul
TI  - ALDH2 protects against stroke by clearing 4-HNE.
PG  - 915-30
LID - 10.1038/cr.2013.69 [doi]
AB  - Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that metabolizes 
      ethanol and toxic aldehydes such as 4-hydroxy-2-nonenal (4-HNE). Using an 
      unbiased proteomic search, we identified ALDH2 deficiency in stroke-prone 
      spontaneously hypertensive rats (SHR-SP) as compared with spontaneously 
      hypertensive rats (SHR). We concluded the causative role of ALDH2 deficiency in 
      neuronal injury as overexpression or activation of ALDH2 conferred 
      neuroprotection by clearing 4-HNE in in vitro studies. Further, ALDH2-knockdown 
      rats revealed the absence of neuroprotective effects of PKCepsilon. Moderate ethanol 
      administration that is known to exert protection against stroke was shown to 
      enhance the detoxification of 4-HNE, and to protect against ischemic cerebral 
      injury through the PKCepsilon-ALDH2 pathway. In SHR-SP, serum 4-HNE level was 
      persistently elevated and correlated inversely with the lifespan. The role of 
      4-HNE in stroke in humans was also suggested by persistent elevation of its 
      plasma levels for at least 6 months after stroke. Lastly, we observed that 21 of 
      1 242 subjects followed for 8 years who developed stroke had higher initial 
      plasma 4-HNE levels than those who did not develop stroke. These findings suggest 
      that activation of the ALDH2 pathway may serve as a useful index in the 
      identification of stroke-prone subjects, and the ALDH2 pathway may be a potential 
      target of therapeutic intervention in stroke.
FAU - Guo, Jin-Min
AU  - Guo JM
AD  - Department of Pharmacology, School of Pharmacy, Second Military Medical 
      University, 325 Guo He Road, Shanghai 200433, China.
FAU - Liu, Ai-Jun
AU  - Liu AJ
FAU - Zang, Pu
AU  - Zang P
FAU - Dong, Wen-Zhe
AU  - Dong WZ
FAU - Ying, Li
AU  - Ying L
FAU - Wang, Wei
AU  - Wang W
FAU - Xu, Pu
AU  - Xu P
FAU - Song, Xu-Rui
AU  - Song XR
FAU - Cai, Jun
AU  - Cai J
FAU - Zhang, She-Qing
AU  - Zhang SQ
FAU - Duan, Jun-Li
AU  - Duan JL
FAU - Mehta, Jawahar L
AU  - Mehta JL
FAU - Su, Ding-Feng
AU  - Su DF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130521
PL  - England
TA  - Cell Res
JT  - Cell research
JID - 9425763
RN  - 0 (Aldehydes)
RN  - 0 (Mitochondrial Proteins)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase)
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase, Mitochondrial)
RN  - EC 1.2.1.3 (Aldh2 protein, rat)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
SB  - IM
CIN - Cell Res. 2013 Jul;23(7):874-5. PMID: 23752927
MH  - Aldehyde Dehydrogenase/genetics/*metabolism
MH  - Aldehyde Dehydrogenase, Mitochondrial
MH  - Aldehydes/*blood/*metabolism
MH  - Animals
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Immunoblotting
MH  - Immunoprecipitation
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Mitochondrial Proteins/genetics/*metabolism
MH  - Oxidative Stress/genetics/physiology
MH  - PC12 Cells
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stroke/blood/*metabolism
PMC - PMC3698638
EDAT- 2013/05/22 06:00
MHDA- 2014/02/01 06:00
PMCR- 2013/07/01
CRDT- 2013/05/22 06:00
PHST- 2012/12/16 00:00 [received]
PHST- 2013/02/05 00:00 [revised]
PHST- 2013/03/20 00:00 [accepted]
PHST- 2013/05/22 06:00 [entrez]
PHST- 2013/05/22 06:00 [pubmed]
PHST- 2014/02/01 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - cr201369 [pii]
AID - 10.1038/cr.2013.69 [doi]
PST - ppublish
SO  - Cell Res. 2013 Jul;23(7):915-30. doi: 10.1038/cr.2013.69. Epub 2013 May 21.