RGD Reference Report - Lipoxin A4 ameliorates cerebral ischaemia/reperfusion injury through upregulation of nuclear factor erythroid 2-related factor 2. - Rat Genome Database
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Lipoxin A4 ameliorates cerebral ischaemia/reperfusion injury through upregulation of nuclear factor erythroid 2-related factor 2.

Authors: Wu, L  Liu, ZJ  Miao, S  Zou, LB  Cai, L  Wu, P  Ye du, Y  Wu, Q  Li, HH 
Citation: Wu L, etal., Neurol Res. 2013 Nov;35(9):968-75. doi: 10.1179/1743132813Y.0000000242. Epub 2013 Jul 22.
RGD ID: 10412696
Pubmed: (View Article at PubMed) PMID:23880501
DOI: Full-text: DOI:10.1179/1743132813Y.0000000242

OBJECTIVES: Lipoxin A4 (LXA4) is a potent anti-inflammatory mediator that exerts a neuroprotective effect following cerebral ischaemia/reperfusion (I/R) injury. However, little is known about the underlying mechanisms. Upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) is generally considered to reduce cerebral I/R injury. Nuclear factor erythroid 2-related factor 2 can induce haeme oxygenase-1 (HO-1) and glutathione (GSH) expression to combat increased oxidative stress. The present study aimed to investigate the effects of Nrf2 signalling on LXA4-mediated neuroprotection. METHODS: Adult male Sprague Dawley rats were subjected to 2-hour middle cerebral artery occlusion followed by 24-hour reperfusion. Rats were randomly divided into four groups: Sham, I/R, LXA4, and LXA4+butoxycarbonyl-Phe-Leu-Phe-Leu-Phe (Boc2) (all n = 24). Brain infarction was detected by 2,3,5-triphenyltetrazolium chloride staining. After 24 hours of reperfusion, Nrf2, HO-1, and p62 expression levels were determined by western blot, and GSH synthesis was assessed. RESULTS: Lipoxin A4 effectively reduced infarct volumes and improved neurological scores. These effects were partially blocked by Boc2, a specific antagonist of the LXA4 receptor (ALXR). Lipoxin A4 induced Nrf2 expression and its nuclear translocation, as well as HO-1 expression and GSH synthesis; Boc2 did not block these effects. The excess p62 accumulation induced by LXA4 might be closely related to Nrf2 activation. DISCUSSION: Overall, our data suggest that Nrf2 upregulation is involved in the neuroprotective effects of LXA4 and may be ALXR independent.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Nfe2l2  (nuclear factor, erythroid 2-like 2)

Genes (Mus musculus)
Nfe2l2  (nuclear factor, erythroid derived 2, like 2)

Genes (Homo sapiens)
NFE2L2  (nuclear factor, erythroid 2 like 2)


Additional Information