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Article: Potential role of α-synuclein and metallothionein in lead-induced inclusion body formation

TitlePotential role of α-synuclein and metallothionein in lead-induced inclusion body formation
Authors
Keywordsα-synuclein
Inclusion bodies
Lead
Metallothionein
MT-null
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://toxsci.oxfordjournals.org/
Citation
Toxicological Sciences, 2009, v. 111 n. 1, p. 100-108 How to Cite?
AbstractLead (Pb) produces aggresome-like inclusion bodies (IBs) in target cells as a toxic response. Our prior work shows metallothionein (MT) is required for this process. We used MT-I/II double knockout (MT-null) and parental wild-type (WT) cell lines to further explore the formation process of Pb-induced IBs. Unlike WT cells, MT-null cells did not form IBs after Pb exposure. Western blot of cytosol showed soluble MT protein in WT cells was lost during Pb exposure as IBs formed. Transfection of MT-I into MT-null cells allowed IBs formation after Pb exposure. Considering Pb-induced IBs may be like disease-related aggresomes, which often contain α-synuclein (Scna), we investigated Scna expression in cells capable (WT) and incapable (MT-null) of producing IBs after Pb exposure. Scna protein showed poor basal expression in MT-null cells. Pb exposure increased Scna expression only in WT cells. MT transfection increased Scna transcript to WT levels. In WT or MT-transfected MT-null cells, Pb-induced Scna expression rapidly increased and then decreased over 48 h as Pb-induced IBs were formed. A direct interaction between Scna and MT was confirmed ex vivo by antibody pulldown assay where the proteins coprecipitated with an antibody to MT. Pb exposure caused increased colocalization of MT and Scna proteins with time only in WT cells. In WT mice after chronic Pb exposure Scna was localized in renal cells containing forming IBs, whereas MT-null mice did not form IBs. Thus, Scna could be component of Pb-induced IBs and, with MT, may play a role in IBs formation.
Persistent Identifierhttp://hdl.handle.net/10722/58101
ISSN
2015 Impact Factor: 3.88
2015 SCImago Journal Rankings: 1.686
ISI Accession Number ID
Funding AgencyGrant Number
National Cancer Institute
National Institutes of HealthNO1-CO-12400
Funding Information:

Federal funds from the National Cancer Institute, National Institutes of Health, under contract (NO1-CO-12400).

References

 

DC FieldValueLanguage
dc.contributor.authorZuo, Pen_HK
dc.contributor.authorQu, Wen_HK
dc.contributor.authorCooper, RNen_HK
dc.contributor.authorGoyer, RAen_HK
dc.contributor.authorDiwan, BAen_HK
dc.contributor.authorWaalkes, MPen_HK
dc.date.accessioned2010-05-31T03:23:49Z-
dc.date.available2010-05-31T03:23:49Z-
dc.date.issued2009en_HK
dc.identifier.citationToxicological Sciences, 2009, v. 111 n. 1, p. 100-108en_HK
dc.identifier.issn1096-6080en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58101-
dc.description.abstractLead (Pb) produces aggresome-like inclusion bodies (IBs) in target cells as a toxic response. Our prior work shows metallothionein (MT) is required for this process. We used MT-I/II double knockout (MT-null) and parental wild-type (WT) cell lines to further explore the formation process of Pb-induced IBs. Unlike WT cells, MT-null cells did not form IBs after Pb exposure. Western blot of cytosol showed soluble MT protein in WT cells was lost during Pb exposure as IBs formed. Transfection of MT-I into MT-null cells allowed IBs formation after Pb exposure. Considering Pb-induced IBs may be like disease-related aggresomes, which often contain α-synuclein (Scna), we investigated Scna expression in cells capable (WT) and incapable (MT-null) of producing IBs after Pb exposure. Scna protein showed poor basal expression in MT-null cells. Pb exposure increased Scna expression only in WT cells. MT transfection increased Scna transcript to WT levels. In WT or MT-transfected MT-null cells, Pb-induced Scna expression rapidly increased and then decreased over 48 h as Pb-induced IBs were formed. A direct interaction between Scna and MT was confirmed ex vivo by antibody pulldown assay where the proteins coprecipitated with an antibody to MT. Pb exposure caused increased colocalization of MT and Scna proteins with time only in WT cells. In WT mice after chronic Pb exposure Scna was localized in renal cells containing forming IBs, whereas MT-null mice did not form IBs. Thus, Scna could be component of Pb-induced IBs and, with MT, may play a role in IBs formation.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://toxsci.oxfordjournals.org/en_HK
dc.relation.ispartofToxicological Sciencesen_HK
dc.rightsToxicological Sciences. Copyright © Oxford University Press.en_HK
dc.subjectα-synucleinen_HK
dc.subjectInclusion bodiesen_HK
dc.subjectLeaden_HK
dc.subjectMetallothioneinen_HK
dc.subjectMT-nullen_HK
dc.titlePotential role of α-synuclein and metallothionein in lead-induced inclusion body formationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1096-6080&volume=111&spage=100&epage=108&date=2009&atitle=Potential+Role+of+{alpha}-Synuclein+and+Metallothionein+in+Lead-Induced+Inclusion+Body+Formationen_HK
dc.identifier.emailZuo, P: peijunzuo@lycos.comen_HK
dc.identifier.authorityZuo, P=rp00050en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/toxsci/kfp132en_HK
dc.identifier.pmid19542206en_HK
dc.identifier.scopuseid_2-s2.0-69049097155en_HK
dc.identifier.hkuros156748en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-69049097155&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume111en_HK
dc.identifier.issue1en_HK
dc.identifier.spage100en_HK
dc.identifier.epage108en_HK
dc.identifier.isiWOS:000269002200011-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridZuo, P=36490907500en_HK
dc.identifier.scopusauthoridQu, W=7102133096en_HK
dc.identifier.scopusauthoridCooper, RN=23008220000en_HK
dc.identifier.scopusauthoridGoyer, RA=35516858600en_HK
dc.identifier.scopusauthoridDiwan, BA=35428217700en_HK
dc.identifier.scopusauthoridWaalkes, MP=7103178453en_HK

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