Differential expression of sPLA2 following spinal cord injury and a functional role for sPLA2-IIA in mediating oligodendrocyte death

dc.contributor.authorTitsworth, W. Lee
dc.contributor.authorCheng, Xiaoxin
dc.contributor.authorKe, Yan
dc.contributor.authorDeng, Lingxiao
dc.contributor.authorBurckardt, Kenneth A.
dc.contributor.authorPendleton, Chris
dc.contributor.authorLiu, Nai-Kui
dc.contributor.authorShao, Hui
dc.contributor.authorCao, Qi-Lin
dc.contributor.authorXu, Xiao-Ming
dc.contributor.departmentDepartment of Medicine, IU School of Medicineen_US
dc.date.accessioned2015-11-18T18:49:13Z
dc.date.available2015-11-18T18:49:13Z
dc.date.issued2009-11
dc.description.abstractAfter the initial mechanical insult of spinal cord injury (SCI), secondary mediators propagate a massive loss of oligodendrocytes. We previously showed that following SCI both the total phospholipase activity and cytosolic PLA(2)-IV alpha protein expression increased. However, the expression of secreted isoforms of PLA(2) (sPLA(2)) and their possible roles in oligodendrocyte death following SCI remained unclear. Here we report that mRNAs extracted 15 min, 4 h, 1 day, or 1 month after cervical SCI show marked upregulation of sPLA(2)-IIA and IIE at 4 h after injury. In contrast, SCI induced down regulation of sPLA(2)-X, and no change in sPLA(2)-IB, IIC, V, and XIIA expression. At the lesion site, sPLA(2)-IIA and IIE expression were localized to oligodendrocytes. Recombinant human sPLA(2)-IIA (0.01, 0.1, or 2 microM) induced a dose-dependent cytotoxicity in differentiated adult oligodendrocyte precursor cells but not primary astrocytes or Schwann cells in vitro. Most importantly, pretreatment with S3319, a sPLA(2)-IIA inhibitor, before a 30 min H(2)O(2) injury (1 or 10 mM) significantly reduced oligodendrocyte cell death at 48 h. Similarly, pretreatment with S3319 before injury with IL-1 beta and TNFalpha prevented cell death and loss of oligodendrocyte processes at 72 h. Collectively, these findings suggest that sPLA(2)-IIA and IIE are increased following SCI, that increased sPLA(2)-IIA can be cytotoxic to oligodendrocytes, and that in vitro blockade of sPLA(2) can create sparing of oligodendrocytes in two distinct injury models. Therefore, sPLA(2)-IIA may be an important mediator of oligodendrocyte death and a novel target for therapeutic intervention following SCI.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationTitsworth, W. L., Cheng, X., Ke, Y., Deng, L., Burckardt, K. A., Pendleton, C., … Xu, X.-M. (2009). Differential Expression of sPLA2 Following Spinal Cord Injury and a Functional Role for sPLA2-IIA in Mediating Oligodendrocyte Death. Glia, 57(14), 1521–1537. http://doi.org/10.1002/glia.20867en_US
dc.identifier.urihttps://hdl.handle.net/1805/7481
dc.language.isoen_USen_US
dc.publisherWileyen_US
dc.relation.isversionof10.1002/glia.20867en_US
dc.relation.journalGliaen_US
dc.rightsIUPUI Open Access Policyen_US
dc.sourcePMCen_US
dc.subjectAstrocytesen_US
dc.subjectAxonsen_US
dc.subjectNeuronsen_US
dc.subjectPhospholipases Aen_US
dc.subjectIL-1βen_US
dc.subjectTNF-αen_US
dc.subjectH2O2en_US
dc.subjectReactive oxygen speciesen_US
dc.titleDifferential expression of sPLA2 following spinal cord injury and a functional role for sPLA2-IIA in mediating oligodendrocyte deathen_US
dc.typeArticleen_US
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