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Article: Tissue kallikrein protects cortical neurons against in vitro ischemia-acidosis/reperfusion-induced injury through the ERK1/2 pathway

TitleTissue kallikrein protects cortical neurons against in vitro ischemia-acidosis/reperfusion-induced injury through the ERK1/2 pathway
Authors
KeywordsExtracellular signal-regulated kinase1/2 signaling pathways
Acidosis
Acid-sensing ion channels
Cortical neurons
Tissue kallikrein
Oxygen and glucose deprivation
Oxidative stress
Issue Date2009
Citation
Experimental Neurology, 2009, v. 219, n. 2, p. 453-465 How to Cite?
AbstractHuman tissue kallikrein (hTK) gene transfer has been shown to protect neurons against cerebral ischemia/reperfusion (I/R) injury, and exogenous tissue kallikrein (TK) administration can enhance neurogenesis and angiogenesis following focal cortical infarction. Previous studies have reported that acidosis is a common feature of ischemia and plays a critical role in brain injury. However, little is known about the role of TK in ischemia-acidosis-induced injury, which is partially caused by the activation of acid-sensing ion channels (ASICs). Here we report that pretreatment of cultured cortical neurons with TK reduced cell death induced by either acidosis or oxygen and glucose deprivation-acidosis/reoxygenation (OGD-A/R). Immunocytochemical staining revealed that TK largely prevented OGD-A/R-induced neuronal morphological changes. We also observed that TK treatment protected cultured neurons from acidosis and OGD-A/R insults. TK exerted the neuroprotective effects by reducing production of reactive oxygen species (ROS), stabilizing the mitochondrial membrane potential (MMP) and inhibiting caspase-3 activation, and thereby attenuating oxidative stress and apoptosis. In addition, we found that activation of the extracellular signal-regulated kinase1/2 (ERK1/2) signaling cascade but not the PI3K/Akt signaling pathway was required for the survival-promoting effect of TK on neurons exposed to OGD-A/R. Moreover, blockade of ASICs had effects similar to TK administration, suggesting direct or indirect involvement of ASICs in TK protection. In conclusion, TK has antioxidant characteristics and is capable of alleviating ischemia-acidosis/reperfusion-induced injury, inhibiting apoptosis and promoting cell survival in vitro through activating the ERK1/2 signaling pathways. Therefore, TK represents a promising therapeutic strategy for ischemic stroke. © 2009 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/265565
ISSN
2019 Impact Factor: 4.691
2015 SCImago Journal Rankings: 2.427
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, Ling-
dc.contributor.authorZhang, Renliang-
dc.contributor.authorLiu, Kui-
dc.contributor.authorZhou, Houguang-
dc.contributor.authorYang, Xuelian-
dc.contributor.authorLiu, Xinfeng-
dc.contributor.authorTang, Min-
dc.contributor.authorSu, Jinjin-
dc.contributor.authorDong, Qiang-
dc.date.accessioned2018-12-03T01:21:02Z-
dc.date.available2018-12-03T01:21:02Z-
dc.date.issued2009-
dc.identifier.citationExperimental Neurology, 2009, v. 219, n. 2, p. 453-465-
dc.identifier.issn0014-4886-
dc.identifier.urihttp://hdl.handle.net/10722/265565-
dc.description.abstractHuman tissue kallikrein (hTK) gene transfer has been shown to protect neurons against cerebral ischemia/reperfusion (I/R) injury, and exogenous tissue kallikrein (TK) administration can enhance neurogenesis and angiogenesis following focal cortical infarction. Previous studies have reported that acidosis is a common feature of ischemia and plays a critical role in brain injury. However, little is known about the role of TK in ischemia-acidosis-induced injury, which is partially caused by the activation of acid-sensing ion channels (ASICs). Here we report that pretreatment of cultured cortical neurons with TK reduced cell death induced by either acidosis or oxygen and glucose deprivation-acidosis/reoxygenation (OGD-A/R). Immunocytochemical staining revealed that TK largely prevented OGD-A/R-induced neuronal morphological changes. We also observed that TK treatment protected cultured neurons from acidosis and OGD-A/R insults. TK exerted the neuroprotective effects by reducing production of reactive oxygen species (ROS), stabilizing the mitochondrial membrane potential (MMP) and inhibiting caspase-3 activation, and thereby attenuating oxidative stress and apoptosis. In addition, we found that activation of the extracellular signal-regulated kinase1/2 (ERK1/2) signaling cascade but not the PI3K/Akt signaling pathway was required for the survival-promoting effect of TK on neurons exposed to OGD-A/R. Moreover, blockade of ASICs had effects similar to TK administration, suggesting direct or indirect involvement of ASICs in TK protection. In conclusion, TK has antioxidant characteristics and is capable of alleviating ischemia-acidosis/reperfusion-induced injury, inhibiting apoptosis and promoting cell survival in vitro through activating the ERK1/2 signaling pathways. Therefore, TK represents a promising therapeutic strategy for ischemic stroke. © 2009 Elsevier Inc. All rights reserved.-
dc.languageeng-
dc.relation.ispartofExperimental Neurology-
dc.subjectExtracellular signal-regulated kinase1/2 signaling pathways-
dc.subjectAcidosis-
dc.subjectAcid-sensing ion channels-
dc.subjectCortical neurons-
dc.subjectTissue kallikrein-
dc.subjectOxygen and glucose deprivation-
dc.subjectOxidative stress-
dc.titleTissue kallikrein protects cortical neurons against in vitro ischemia-acidosis/reperfusion-induced injury through the ERK1/2 pathway-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.expneurol.2009.06.021-
dc.identifier.pmid19576887-
dc.identifier.scopuseid_2-s2.0-69849111675-
dc.identifier.volume219-
dc.identifier.issue2-
dc.identifier.spage453-
dc.identifier.epage465-
dc.identifier.eissn1090-2430-
dc.identifier.isiWOS:000270157300011-

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