{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/39"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/39","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"A Missing link between lipid metabolism, inflammation and apoptosis: Phospholipase A2-activating protein (PLAA)","abstract":"Phospholipase A2-Activating Protein (PLAA) is a novel signaling molecule that regulates the production of arachidonic acid (AA), prostaglandin E2 (PGE2) and TNF-¦Á. Literature suggests that PLAA could be involved in inflammatory responses and apoptosis. However, the in situ function of PLAA is elusive. To elucidate PLAA¡¯s role in TNF-¦Á-induced inflammatory responses and cisplatin-induced apoptosis, we manipulated the expression of the plaa gene at cellular level using overexpression and siRNA approaches. We generated HeLa (Tet-off) cells overexpressing plaa (plaa high) and control (plaa low) cells. We compared plaa high and plaa low cells for transcriptional profiling and their responses to TNF-¦Á stimulation. Overexpression of the plaa gene induced the expression of the proinflammatory cytokine IL-32 and reduced the expression of annexin A4 (a PLA2 inhibitor) and clusterin. We demonstrated that extracellular clusterin limited the production of PGE2. We showed that upon TNF-¦Á stimulation, plaa high cells revealed enhanced PLA2 activation, COX-2 expression and PGE2 production. Furthermore, we found that in response to TNF-¦Á, plaa high cells had significantly enhanced activation of NF-¦ÊB and production of IL-6, compared to the TNF-¦Á-stimulated plaa low cells. To understand regulation of plaa gene expression, we used a luciferase reporter system in normal HeLa cells and identified one stimulatory element, with Sp1 transcription factor-binding site, and one inhibitory element, in exon 1 of the plaa gene. To determine the role of PLAA in apoptosis, we compared the apoptotic responses to cisplatin in plaa high and plaa low cells. Cisplatin-stimulated plaa high cells contained significantly higher levels of DNA fragmentation, caspase activities, PLA2 enzyme activity and mitochondrial damage than did the cisplatin-stimulated plaa low cells. siRNA against PLAA (siRNA-PLAA) reverted the above mentioned trend and promoted cell viability. Further, cisplatin-stimulated plaa high cells produced less cytoprotecive clusterin and more pro-apoptotic IL-32 than did the cisplatin- stimulated plaa low cells. siRNA-PLAA promoted clusterin production and inhibited IL-32 expression from both plaa high and plaa low cells. Finally, our proteomic analysis revealed that cisplatin-stimulated plaa high cells contained higher levels of phosphorylated JNK/c-Jun and FasL than did cisplatin-stimulated plaa low cells.","abstract_html":"Phospholipase A2-Activating Protein (PLAA) is a novel signaling molecule that regulates the production of arachidonic acid (AA), prostaglandin E2 (PGE2) and TNF-¦Á. Literature suggests that PLAA could be involved in inflammatory responses and apoptosis. However, the in situ function of PLAA is elusive. To elucidate PLAA¡¯s role in TNF-¦Á-induced inflammatory responses and cisplatin-induced apoptosis, we manipulated the expression of the plaa gene at cellular level using overexpression and siRNA approaches. We generated HeLa (Tet-off) cells overexpressing plaa (plaa high) and control (plaa low) cells. We compared plaa high and plaa low cells for transcriptional profiling and their responses to TNF-¦Á stimulation. Overexpression of the plaa gene induced the expression of the proinflammatory cytokine IL-32 and reduced the expression of annexin A4 (a PLA2 inhibitor) and clusterin. We demonstrated that extracellular clusterin limited the production of PGE2. We showed that upon TNF-¦Á stimulation, plaa high cells revealed enhanced PLA2 activation, COX-2 expression and PGE2 production. Furthermore, we found that in response to TNF-¦Á, plaa high cells had significantly enhanced activation of NF-¦ÊB and production of IL-6, compared to the TNF-¦Á-stimulated plaa low cells. To understand regulation of plaa gene expression, we used a luciferase reporter system in normal HeLa cells and identified one stimulatory element, with Sp1 transcription factor-binding site, and one inhibitory element, in exon 1 of the plaa gene. To determine the role of PLAA in apoptosis, we compared the apoptotic responses to cisplatin in plaa high and plaa low cells. Cisplatin-stimulated plaa high cells contained significantly higher levels of DNA fragmentation, caspase activities, PLA2 enzyme activity and mitochondrial damage than did the cisplatin-stimulated plaa low cells. siRNA against PLAA (siRNA-PLAA) reverted the above mentioned trend and promoted cell viability. Further, cisplatin-stimulated plaa high cells produced less cytoprotecive clusterin and more pro-apoptotic IL-32 than did the cisplatin- stimulated plaa low cells. siRNA-PLAA promoted clusterin production and inhibited IL-32 expression from both plaa high and plaa low cells. Finally, our proteomic analysis revealed that cisplatin-stimulated plaa high cells contained higher levels of phosphorylated JNK/c-Jun and FasL than did cisplatin-stimulated plaa low cells.","abstract_has_math":false,"creators":["Fan Zhang"],"institution":"The University of Texas Medical Branch","degree_name":"PhD","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Ashok K. Chopra"],"committee_chairs":[],"committee_members":["Thomas G. Wood","Sheila E. Crowe","Johnny W. Peterson","Istvan Boldogh"],"year":2009,"date_issued":"2009-03-02","date_published":"2009-03-02","updated_at":"2026-07-24T05:50:54Z","subjects":["prostanoid","phospholipid","Phospholipase A2","lipid metabolism","inflammation"],"languages":["eng"],"rights":["Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-03112009-215005"],"render_values":[{"text":"etd-03112009-215005","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2152.3/39","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Ashok K. Chopra"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Thomas G. Wood","Sheila E. Crowe","Johnny W. Peterson","Istvan Boldogh"]},{"key":"dc:creator","label":"Author","values":["Fan Zhang"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2011-12-20T16:04:17Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2010-09-28","2011-12-20T16:04:17Z"]},{"key":"dc:date.issued","label":"Date","values":["2009-03-02"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["PhD"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["prostanoid","phospholipid","Phospholipase A2","lipid metabolism","inflammation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-03112009-215005"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2152.3/39"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Phospholipase A2-Activating Protein (PLAA) is a novel signaling molecule that regulates the production of arachidonic acid (AA), prostaglandin E2 (PGE2) and TNF-¦Á. Literature suggests that PLAA could be involved in inflammatory responses and apoptosis. However, the in situ function of PLAA is elusive. To elucidate PLAA¡¯s role in TNF-¦Á-induced inflammatory responses and cisplatin-induced apoptosis, we manipulated the expression of the plaa gene at cellular level using overexpression and siRNA approaches. We generated HeLa (Tet-off) cells overexpressing plaa (plaa high) and control (plaa low) cells. We compared plaa high and plaa low cells for transcriptional profiling and their responses to TNF-¦Á stimulation. Overexpression of the plaa gene induced the expression of the proinflammatory cytokine IL-32 and reduced the expression of annexin A4 (a PLA2 inhibitor) and clusterin. We demonstrated that extracellular clusterin limited the production of PGE2. We showed that upon TNF-¦Á stimulation, plaa high cells revealed enhanced PLA2 activation, COX-2 expression and PGE2 production. Furthermore, we found that in response to TNF-¦Á, plaa high cells had significantly enhanced activation of NF-¦ÊB and production of IL-6, compared to the TNF-¦Á-stimulated plaa low cells. To understand regulation of plaa gene expression, we used a luciferase reporter system in normal HeLa cells and identified one stimulatory element, with Sp1 transcription factor-binding site, and one inhibitory element, in exon 1 of the plaa gene. To determine the role of PLAA in apoptosis, we compared the apoptotic responses to cisplatin in plaa high and plaa low cells. Cisplatin-stimulated plaa high cells contained significantly higher levels of DNA fragmentation, caspase activities, PLA2 enzyme activity and mitochondrial damage than did the cisplatin-stimulated plaa low cells. siRNA against PLAA (siRNA-PLAA) reverted the above mentioned trend and promoted cell viability. Further, cisplatin-stimulated plaa high cells produced less cytoprotecive clusterin and more pro-apoptotic IL-32 than did the cisplatin- stimulated plaa low cells. siRNA-PLAA promoted clusterin production and inhibited IL-32 expression from both plaa high and plaa low cells. Finally, our proteomic analysis revealed that cisplatin-stimulated plaa high cells contained higher levels of phosphorylated JNK/c-Jun and FasL than did cisplatin-stimulated plaa low cells."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["electronic"]},{"key":"dc:title","label":"Title","values":["A Missing link between lipid metabolism, inflammation and apoptosis: Phospholipase A2-activating protein (PLAA)"]}]}],"canonical_facts":{"dc:contributor.advisor":["Ashok K. Chopra"],"dc:contributor.committeemember":["Thomas G. Wood","Sheila E. Crowe","Johnny W. Peterson","Istvan Boldogh"],"dc:creator":["Fan Zhang"],"dc:date.accessioned":["2011-12-20T16:04:17Z"],"dc:date.available":["2010-09-28","2011-12-20T16:04:17Z"],"dc:date.issued":["2009-03-02"],"dc:description.abstract":["Phospholipase A2-Activating Protein (PLAA) is a novel signaling molecule that regulates the production of arachidonic acid (AA), prostaglandin E2 (PGE2) and TNF-¦Á. Literature suggests that PLAA could be involved in inflammatory responses and apoptosis. However, the in situ function of PLAA is elusive. To elucidate PLAA¡¯s role in TNF-¦Á-induced inflammatory responses and cisplatin-induced apoptosis, we manipulated the expression of the plaa gene at cellular level using overexpression and siRNA approaches. We generated HeLa (Tet-off) cells overexpressing plaa (plaa high) and control (plaa low) cells. We compared plaa high and plaa low cells for transcriptional profiling and their responses to TNF-¦Á stimulation. Overexpression of the plaa gene induced the expression of the proinflammatory cytokine IL-32 and reduced the expression of annexin A4 (a PLA2 inhibitor) and clusterin. We demonstrated that extracellular clusterin limited the production of PGE2. We showed that upon TNF-¦Á stimulation, plaa high cells revealed enhanced PLA2 activation, COX-2 expression and PGE2 production. Furthermore, we found that in response to TNF-¦Á, plaa high cells had significantly enhanced activation of NF-¦ÊB and production of IL-6, compared to the TNF-¦Á-stimulated plaa low cells. To understand regulation of plaa gene expression, we used a luciferase reporter system in normal HeLa cells and identified one stimulatory element, with Sp1 transcription factor-binding site, and one inhibitory element, in exon 1 of the plaa gene. To determine the role of PLAA in apoptosis, we compared the apoptotic responses to cisplatin in plaa high and plaa low cells. Cisplatin-stimulated plaa high cells contained significantly higher levels of DNA fragmentation, caspase activities, PLA2 enzyme activity and mitochondrial damage than did the cisplatin-stimulated plaa low cells. siRNA against PLAA (siRNA-PLAA) reverted the above mentioned trend and promoted cell viability. Further, cisplatin-stimulated plaa high cells produced less cytoprotecive clusterin and more pro-apoptotic IL-32 than did the cisplatin- stimulated plaa low cells. siRNA-PLAA promoted clusterin production and inhibited IL-32 expression from both plaa high and plaa low cells. Finally, our proteomic analysis revealed that cisplatin-stimulated plaa high cells contained higher levels of phosphorylated JNK/c-Jun and FasL than did cisplatin-stimulated plaa low cells."],"dc:format.medium":["electronic"],"dc:identifier.other":["etd-03112009-215005"],"dc:identifier.uri":["http://hdl.handle.net/2152.3/39"],"dc:language.iso":["eng"],"dc:rights":["Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works."],"dc:subject":["prostanoid","phospholipid","Phospholipase A2","lipid metabolism","inflammation"],"dc:title":["A Missing link between lipid metabolism, inflammation and apoptosis: Phospholipase A2-activating protein (PLAA)"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["PhD"],"thesis:institution_name":["The University of Texas Medical Branch"]},"updated_at":"2026-07-24T05:50:54Z"}