PMID- 22325100
OWN - NLM
STAT- MEDLINE
DCOM- 20121113
LR  - 20161125
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1445
DP  - 2012 Mar 22
TI  - The protective effect of nordihydroguaiaretic acid on cerebral 
      ischemia/reperfusion injury is mediated by the JNK pathway.
PG  - 73-81
LID - 10.1016/j.brainres.2012.01.031 [doi]
AB  - Nordihydroguaiaretic acid (NDGA) is a powerful antioxidant and/or lipoxygenase 
      (LOX) inhibitor which is isolated from Larrea tridentate. NDGA has been shown to 
      have neuroprotective effects both in vitro and in vivo experiments. However, 
      little is known regarding NDGA's protective mechanism in ischemia/reperfusion 
      (I/R) injury. We therefore investigated the potential protective effects of NDGA 
      and explored the underlying mechanisms. Oxygen-glucose deprivation (OGD) was 
      performed in cultured rat cortical neurons for 60min. The effect of NDGA on OGD 
      induced cell death and apoptosis was examined at 24h after reperfusion. Western 
      blot was used to analyze the expression of p-c-jun and p-JNK. Exogenous 5-, 12-, 
      15-hydroxyeicosatetraenoic acid (HETE) was added respectively to the cells to 
      investigate the contribution of the products of LOX to the c-Jun N-terminal 
      protein kinase (JNK) pathway. Rats were injected intraperitoneally with NDGA 
      before being subjected to middle cerebral artery occlusion (MCAO). At 24h after 
      reperfusion, neurological deficit, brain infarct volume and the expression of 
      p-c-jun and p-JNK were measured. The results showed that NDGA increased cell 
      viability and inhibited apoptosis after OGD in neurons. NDGA suppressed the 
      expression of p-c-jun and p-JNK in cortical neurons, whereas exogenous 12-, 
      15-HETE attenuated this effect. NDGA improved neurological deficit, reduced 
      infarct volumes, and downregulated the overexpression of p-c-jun and p-JNK after 
      MCAO and reperfusion. In conclusion, these results suggest that NDGA's protective 
      effect against I/R injury is mediated by the suppression of JNK pathway. This 
      effect is probably due to its 12/15-LOX inhibitor property.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Liu, Yu
AU  - Liu Y
AD  - Department of Neurology, the Second Affiliated Hospital of Harbin Medical 
      University, 246 Xuefu Road, Harbin, Heilongjiang 150086, China.
FAU - Wang, Huan
AU  - Wang H
FAU - Zhu, Yanmei
AU  - Zhu Y
FAU - Chen, Li
AU  - Chen L
FAU - Qu, Youyang
AU  - Qu Y
FAU - Zhu, Yulan
AU  - Zhu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120124
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 7BO8G1BYQU (Masoprocol)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Brain Infarction/etiology/prevention & control
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Disease Models, Animal
MH  - Embryo, Mammalian
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Glucose/deficiency
MH  - Hydroxyeicosatetraenoic Acids/pharmacology
MH  - Hypoxia/drug therapy
MH  - In Situ Nick-End Labeling
MH  - *Infarction, Middle Cerebral Artery/complications/drug therapy/metabolism
MH  - MAP Kinase Kinase 4/metabolism
MH  - MAP Kinase Signaling System/*drug effects/physiology
MH  - Masoprocol/*therapeutic use
MH  - Nervous System Diseases/etiology/*prevention & control
MH  - Neurologic Examination
MH  - Neurons/drug effects/enzymology
MH  - Neuroprotective Agents/*therapeutic use
MH  - Proto-Oncogene Proteins c-jun/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/complications/drug therapy/metabolism
EDAT- 2012/02/14 06:00
MHDA- 2012/11/14 06:00
CRDT- 2012/02/14 06:00
PHST- 2011/09/27 00:00 [received]
PHST- 2012/01/09 00:00 [revised]
PHST- 2012/01/13 00:00 [accepted]
PHST- 2012/02/14 06:00 [entrez]
PHST- 2012/02/14 06:00 [pubmed]
PHST- 2012/11/14 06:00 [medline]
AID - S0006-8993(12)00092-3 [pii]
AID - 10.1016/j.brainres.2012.01.031 [doi]
PST - ppublish
SO  - Brain Res. 2012 Mar 22;1445:73-81. doi: 10.1016/j.brainres.2012.01.031. Epub 2012 
      Jan 24.