Abstract | 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: 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:
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Authors | Le Wu, Zi Jian Liu, Sen Miao, Lin Bing Zou, Lei Cai, Ping Wu, Du Yun Ye, Qiang Wu, Hong Hua Li |
Journal | Neurological research
(Neurol Res)
Vol. 35
Issue 9
Pg. 968-75
(Nov 2013)
ISSN: 1743-1328 [Electronic] England |
PMID | 23880501
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Heat-Shock Proteins
- Lipoxins
- NF-E2-Related Factor 2
- Neuroprotective Agents
- Nfe2l2 protein, rat
- Oligopeptides
- Sequestosome-1 Protein
- Sqstm1 protein, rat
- lipoxin A4
- butyloxycarbonyl-phenylalanyl-leucyl-phenylalanyl-leucyl-phenylalanine
- Heme Oxygenase (Decyclizing)
- Hmox1 protein, rat
- Glutathione
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Topics |
- Animals
- Blotting, Western
- Brain
(metabolism, pathology)
- Glutathione
(metabolism)
- Heat-Shock Proteins
(metabolism)
- Heme Oxygenase (Decyclizing)
(metabolism)
- Infarction, Middle Cerebral Artery
(drug therapy, metabolism, pathology)
- Lipoxins
(therapeutic use)
- Male
- NF-E2-Related Factor 2
(metabolism)
- Neuroprotective Agents
(therapeutic use)
- Oligopeptides
(pharmacology)
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- Reperfusion Injury
(drug therapy, metabolism, pathology)
- Sequestosome-1 Protein
- Severity of Illness Index
- Up-Regulation
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