Isoflurane Postconditioning Inhibits tPA-Induced Matrix Metalloproteinases Activation After Hypoxic Injury via Low-Density Lipoprotein Receptor-Related Protein and Extracellular Signal-Regulated Kinase Pathway

被引：14

作者：

Kim, So Yeon ^{[1
]}

Cheon, So Yeong ^{[1
]}

Kim, Eun Jung ^{[1
]}

Lee, Jae Hoon ^{[1
]}

Kam, Eun Hee ^{[1
]}

Kim, Jeong Min ^{[1
]}

Park, Miran ^{[1
]}

Koo, Bon-Nyeo ^{[1
]}

机构：

[1] Yonsei Univ, Anesthesia & Pain Res Inst, Dept Anesthesiol & Pain Med, Coll Med, 50-1 Yonsei Ro, Seoul 03722, South Korea

来源：

NEUROCHEMICAL RESEARCH | 2017年 / 42卷 / 05期

基金：

新加坡国家研究基金会;

关键词：

Extracellular signal-regulated kinase; Hypoxia; Isoflurane; Low-density lipoprotein receptor-related protein; Matrix metalloproteinase; Tissue plasminogen activator; TISSUE-PLASMINOGEN ACTIVATOR; BLOOD-BRAIN-BARRIER; ACUTE ISCHEMIC-STROKE; OXYGEN-GLUCOSE DEPRIVATION; CEREBRAL-ISCHEMIA; IN-VITRO; INTRACELLULAR CA2+; REPERFUSION INJURY; RATS; NEUROPROTECTION;

D O I：

10.1007/s11064-017-2211-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tissue plasminogen activator (tPA) is the only recommended pharmacological treatment for acute ischemic stroke. However, tPA can induce intracerebral hemorrhage by blood-brain barrier breakdown through an increase in matrix metalloproteinases (MMPs). Previously, we showed that isoflurane postconditioning reduced intracranial hemorrhage following tPA treatment after cerebral ischemia. Here, we investigated the mechanism by which isoflurane postconditioning reduces tPA-induced MMP-2 and MMP-9 activation following hypoxia/reoxygenation (H/R) in brain endothelial cells. Mouse brain endothelial cells (bEnd.3) were exposed to 6 h of oxygen-glucose deprivation and 3 h of reoxygenation with tPA. Cells were treated with isoflurane for 1 h of the reoxygenation condition and the effect of isoflurane postconditioning on MMP-2 and MMP-9 activation was assessed. Involvement of low-density lipoprotein receptor-related protein (LRP), which is a receptor for tPA, and the extracellular signal-regulated kinase (ERK) and NF-kappa B pathway in isoflurane postconditioning was assessed using LRP inhibitor (receptor-associated protein, RAP) and ERK-1/2 inhibitor (PD98059). Isoflurane postconditioning decreased tPA-induced MMP-2 and MMP-9 activation under H/R. tPA treatment under H/R increased expression of LRP and the active form of NF-kappa B. Isoflurane postconditioning suppressed LRP expression, increased ERK-1/2 activation, and suppressed MMP-2 and MMP-9 activation, comparable to the effect of RAP. Activation of ERK-1/2, inhibition of NF-kappa B activation, and suppression of MMP-2 and MMP-9 activation by isoflurane postconditioning were abolished with PD98059 treatment. These finding indicate that isoflurane postconditioning inhibits tPA-induced MMP-2 and MMP-9 activation following H/R via the LRP/ERK/NF-kappa B pathway in bEnd.3.

引用

页码：1533 / 1542

页数：10

共 41 条

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