AUB ScholarWorks

Degradation of βII-Spectrin Protein by Calpain-2 and Caspase-3 Under Neurotoxic and Traumatic Brain Injury Conditions

Show simple item record

dc.contributor.author Kobeissy F.H.
dc.contributor.author Liu M.C.
dc.contributor.author Yang Z.
dc.contributor.author Zhang Z.
dc.contributor.author Zheng W.
dc.contributor.author Glushakova O.
dc.contributor.author Mondello S.
dc.contributor.author Anagli J.
dc.contributor.author Hayes R.L.
dc.contributor.author Wang K.K.W.
dc.contributor.editor
dc.date 2014
dc.date.accessioned 2017-10-05T15:30:58Z
dc.date.available 2017-10-05T15:30:58Z
dc.date.issued 2014
dc.identifier 10.1007/s12035-014-8898-z
dc.identifier.isbn
dc.identifier.issn 08937648
dc.identifier.uri http://hdl.handle.net/10938/15311
dc.description.abstract A major consequence of traumatic brain injury (TBI) is the rapid proteolytic degradation of structural cytoskeletal proteins. This process is largely reflected by the interruption of axonal transport as a result of extensive axonal injury leading to neuronal cell injury. Previous work from our group has described the extensive degradation of the axonally enriched cytoskeletal αII-spectrin protein which results in molecular signature breakdown products (BDPs) indicative of injury mechanisms and to specific protease activation both in vitro and in vivo. In the current study, we investigated the integrity of βII-spectrin protein and its proteolytic profile both in primary rat cerebrocortical cell culture under apoptotic, necrotic, and excitotoxic challenge and extended to in vivo rat model of experimental TBI (controlled cortical impact model). Interestingly, our results revealed that the intact 260-kDa βII-spectrin is degraded into major fragments (βII-spectrin breakdown products (βsBDPs)) of 110, 108, 85, and 80 kDa in rat brain (hippocampus and cortex) 48 h post-injury. These βsBDP profiles were further characterized and compared to an in vitro βII-spectrin fragmentation pattern of naive rat cortex lysate digested by calpain-2 and caspase-3. Results revealed that βII-spectrin was degraded into major fragments of 110-85 kDa by calpain-2 activation and 108-80 kDa by caspase-3 activation. These data strongly support the hypothesis that in vivo activation of multiple protease system induces structural protein proteolysis involving βII-spectrin proteolysis via a specific calpain and-or caspase-mediated pathway resulting in a signature, protease-specific βsBDPs that are dependent upon the type of neural injury mechanism. This work extends on previous published work that discusses the interplay spectrin family (αII-spectrin and βII-spectrin) and their susceptibility to protease proteolysis and their implication to neuronal cell death mechanisms.
dc.format.extent
dc.language English
dc.publisher Humana Press Inc.;
dc.relation.ispartof Publication Name: Molecular Neurobiology; Publication Year: 2014;
dc.relation.ispartofseries
dc.relation.uri
dc.source Scopus
dc.subject.other
dc.title Degradation of βII-Spectrin Protein by Calpain-2 and Caspase-3 Under Neurotoxic and Traumatic Brain Injury Conditions
dc.type Article in Press
dc.contributor.affiliation Kobeissy, F.H., Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry, University of FloridaGainesville, FL, United States, Faculty of Medicine, Department of Biochemistry and Molecular Genetics, American University of BeirutBeirut, Lebanon
dc.contributor.affiliation Liu, M.C., Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry, University of FloridaGainesville, FL, United States
dc.contributor.affiliation Yang, Z., Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry, University of FloridaGainesville, FL, United States
dc.contributor.affiliation Zhang, Z., Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry, University of FloridaGainesville, FL, United States
dc.contributor.affiliation Zheng, W., Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry, University of FloridaGainesville, FL, United States
dc.contributor.affiliation Glushakova, O., Banyan Laboratory, Banyan Biomarkers, Inc.Alachua, FL, United States
dc.contributor.affiliation Mondello, S., Department of Neurosciences, University of MessinaMessina, Italy
dc.contributor.affiliation Anagli, J., Banyan Laboratory, Banyan Biomarkers, Inc.Alachua, FL, United States
dc.contributor.affiliation Hayes, R.L., Banyan Laboratory, Banyan Biomarkers, Inc.Alachua, FL, United States
dc.contributor.affiliation Wang, K.K.W., Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry, University of FloridaGainesville, FL, United States
dc.contributor.authorAddress Kobeissy, F.H.; Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry, University of FloridaUnited States
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Biochemistry and Molecular Genetics;
dc.contributor.authorDepartment Biochemistry and Molecular Genetics
dc.contributor.authorDivision
dc.contributor.authorEmail
dc.contributor.authorFaculty Faculty of Medicine
dc.contributor.authorInitials
dc.contributor.authorOrcidID
dc.contributor.authorReprintAddress
dc.contributor.authorResearcherID
dc.contributor.authorUniversity American University of Beirut Medical Center
dc.description.cited
dc.description.citedCount
dc.description.citedTotWOSCount
dc.description.citedWOSCount
dc.format.extentCount 1
dc.identifier.articleNo
dc.identifier.coden MONBE
dc.identifier.pubmedID
dc.identifier.scopusID 84907646116
dc.identifier.url
dc.publisher.address
dc.relation.ispartofConference
dc.relation.ispartofConferenceCode
dc.relation.ispartofConferenceDate
dc.relation.ispartofConferenceHosting
dc.relation.ispartofConferenceLoc
dc.relation.ispartofConferenceSponsor
dc.relation.ispartofConferenceTitle
dc.relation.ispartofFundingAgency
dc.relation.ispartOfISOAbbr
dc.relation.ispartOfIssue
dc.relation.ispartOfPart
dc.relation.ispartofPubTitle Molecular Neurobiology
dc.relation.ispartofPubTitleAbbr Mol. Neurobiol.
dc.relation.ispartOfSpecialIssue
dc.relation.ispartOfSuppl
dc.relation.ispartOfVolume
dc.source.ID
dc.type.publication Journal
dc.subject.otherAuthKeyword Calpain-2
dc.subject.otherAuthKeyword Caspase-3
dc.subject.otherAuthKeyword Cell death
dc.subject.otherAuthKeyword Neurodegeneration
dc.subject.otherAuthKeyword Protease
dc.subject.otherAuthKeyword TBI
dc.subject.otherAuthKeyword βII-Spectrin apoptotic
dc.subject.otherChemCAS
dc.subject.otherIndex
dc.subject.otherKeywordPlus
dc.subject.otherWOS


Files in this item

Files Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

Search AUB ScholarWorks


Browse

My Account