File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: p38 MAP kinase is involved in lipopolysaccharide-induced dopaminergic neuronal cell death in rat mesencephalic neuron-glia cultures

Titlep38 MAP kinase is involved in lipopolysaccharide-induced dopaminergic neuronal cell death in rat mesencephalic neuron-glia cultures
Authors
Issue Date2002
PublisherWiley-Blackwell Publishing, Inc. The Journal's web site is located at http://www.blackwellpublishing.com/journal.asp?ref=0077-8923&site=1
Citation
Annals Of The New York Academy Of Sciences, 2002, v. 962, p. 332-346 How to Cite?
AbstractImmune stimulants, such as the bacterial endotoxin, lipopolysaccharide (LPS), the human immunodeficiency virus-1 coat protein gp120, or β-amyloid peptides, lead to glial activation and production of various immune mediators, such as nitric oxide (NO) and proinflammatory cytokines in the brain. These mediators appear to contribute to neuronal cell death in neurodegenerative diseases. However, the signaling pathways, which mediate the neurotoxic effect by the endotoxin, are not understood. The purpose of this study was to determine the role of mitogen-activated protein kinase (MAPK) in LPS-induced neurodegeneration using mesencephalic dopaminergic neuron/glia cultures. We have found that the p38 MAPK is important in LPS-induced death of mesencephalic neurons in rat neuron-glia mixed cultures. Upon treatment with 10 ng/ml LPS, the number of dopaminergic neurons decreased by 80% within 48 h, preceded by a significant production of NO by glia. Neuroprotection by selective inhibition of p38 MAPK activity paralleled a decrease in LPS-induced inducible nitric oxide synthase (iNOS) expression. These events were significantly reduced by the selective p38 MAPK inhibitor, SB202190, but not by the inactive analogue SB202474. Inhibition of iNOS activity and NO production by treatment with GW274150 was also neuroprotective. Although the p38 MAPK inhibitor afforded significant neuroprotection from LPS toxicity in the neuron-glia mixed culture, it failed to protect dopaminergic neurons from 6-hydroxy-dopamine-induced toxicity, which acts directly on dopaminergic neurons by inducing hydroxyl radical formation from the mitochondria. The results suggest that p38 MAPK in glia plays a significant role in the LPS-induced death of mesencephalic neurons through induction of nitric oxide synthase and resulting NO production.
Persistent Identifierhttp://hdl.handle.net/10722/67739
ISSN
2015 Impact Factor: 4.518
2015 SCImago Journal Rankings: 2.389
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorJeohn, GHen_HK
dc.contributor.authorCooper, CLen_HK
dc.contributor.authorWilson, Ben_HK
dc.contributor.authorChang, RCCen_HK
dc.contributor.authorJang, KJen_HK
dc.contributor.authorKim, HCen_HK
dc.contributor.authorLiu, Ben_HK
dc.contributor.authorHong, JSen_HK
dc.date.accessioned2010-09-06T05:57:49Z-
dc.date.available2010-09-06T05:57:49Z-
dc.date.issued2002en_HK
dc.identifier.citationAnnals Of The New York Academy Of Sciences, 2002, v. 962, p. 332-346en_HK
dc.identifier.issn0077-8923en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67739-
dc.description.abstractImmune stimulants, such as the bacterial endotoxin, lipopolysaccharide (LPS), the human immunodeficiency virus-1 coat protein gp120, or β-amyloid peptides, lead to glial activation and production of various immune mediators, such as nitric oxide (NO) and proinflammatory cytokines in the brain. These mediators appear to contribute to neuronal cell death in neurodegenerative diseases. However, the signaling pathways, which mediate the neurotoxic effect by the endotoxin, are not understood. The purpose of this study was to determine the role of mitogen-activated protein kinase (MAPK) in LPS-induced neurodegeneration using mesencephalic dopaminergic neuron/glia cultures. We have found that the p38 MAPK is important in LPS-induced death of mesencephalic neurons in rat neuron-glia mixed cultures. Upon treatment with 10 ng/ml LPS, the number of dopaminergic neurons decreased by 80% within 48 h, preceded by a significant production of NO by glia. Neuroprotection by selective inhibition of p38 MAPK activity paralleled a decrease in LPS-induced inducible nitric oxide synthase (iNOS) expression. These events were significantly reduced by the selective p38 MAPK inhibitor, SB202190, but not by the inactive analogue SB202474. Inhibition of iNOS activity and NO production by treatment with GW274150 was also neuroprotective. Although the p38 MAPK inhibitor afforded significant neuroprotection from LPS toxicity in the neuron-glia mixed culture, it failed to protect dopaminergic neurons from 6-hydroxy-dopamine-induced toxicity, which acts directly on dopaminergic neurons by inducing hydroxyl radical formation from the mitochondria. The results suggest that p38 MAPK in glia plays a significant role in the LPS-induced death of mesencephalic neurons through induction of nitric oxide synthase and resulting NO production.en_HK
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing, Inc. The Journal's web site is located at http://www.blackwellpublishing.com/journal.asp?ref=0077-8923&site=1en_HK
dc.relation.ispartofAnnals of the New York Academy of Sciencesen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshCell Deathen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshDopamine - metabolismen_HK
dc.subject.meshEnzyme Inhibitors - pharmacologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLipopolysaccharides - pharmacologyen_HK
dc.subject.meshMesencephalon - cytologyen_HK
dc.subject.meshMitogen-Activated Protein Kinases - antagonists & inhibitors - metabolismen_HK
dc.subject.meshNeuroglia - cytology - drug effects - metabolismen_HK
dc.subject.meshNeurons - cytology - drug effects - metabolismen_HK
dc.subject.meshNeuroprotective Agents - pharmacologyen_HK
dc.subject.meshNitric Oxide - metabolismen_HK
dc.subject.meshNitric Oxide Synthase - genetics - metabolismen_HK
dc.subject.meshNitric Oxide Synthase Type IIen_HK
dc.subject.meshOxidopamine - pharmacologyen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Inbred F344en_HK
dc.subject.meshSympatholytics - pharmacologyen_HK
dc.subject.meshp38 Mitogen-Activated Protein Kinasesen_HK
dc.titlep38 MAP kinase is involved in lipopolysaccharide-induced dopaminergic neuronal cell death in rat mesencephalic neuron-glia culturesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0077-8923&volume=962&spage=332&epage=346&date=2002&atitle=p38+MAP+kinase+is+involved+in+lipopolysaccharide-induced+dopaminergic+neuronal+cell+death+in+rat+mesencephalic+neuron-glia+culturesen_HK
dc.identifier.emailChang, RCC:rccchang@hkucc.hku.hken_HK
dc.identifier.authorityChang, RCC=rp00470en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid12076985-
dc.identifier.scopuseid_2-s2.0-0036275058en_HK
dc.identifier.hkuros74662en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036275058&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume962en_HK
dc.identifier.spage332en_HK
dc.identifier.epage346en_HK
dc.identifier.isiWOS:000176952400028-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridJeohn, GH=6602725495en_HK
dc.identifier.scopusauthoridCooper, CL=7403319046en_HK
dc.identifier.scopusauthoridWilson, B=35243580200en_HK
dc.identifier.scopusauthoridChang, RCC=7403713410en_HK
dc.identifier.scopusauthoridJang, KJ=12242617200en_HK
dc.identifier.scopusauthoridKim, HC=36065569300en_HK
dc.identifier.scopusauthoridLiu, B=36079151900en_HK
dc.identifier.scopusauthoridHong, JS=34770185100en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats