{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/86311"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/86311","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Angiotensin Type-2 (At2) Receptor Modulation of Nmda-Mediated Current, Signaling and Apoptosis","abstract":"In the current study, we examined whether treatment with Ang II regulates NMDA-mediated current, signaling and apoptosis. Western blot analysis revealed that Ang II, acting primarily through AT2 receptor activation of the protein phosphatase 2A (PP2A), attenuated NMDA-mediated increases in extracellular regulated kinase-2 (ERK-2) activity. We have identified that AT2 receptor activation inhibits cleavage of the DNA repair enzyme poly-(ADP-ribose) polymerase (PARP) following treatment with NMDA. Inhibition of ERK with MEK inhibitors (PD98059 and U0126) significantly decreased PARP cleavage (cPARP), while inhibition of PP2A with 10 nM okadaic acid, significantly increased NMDA-mediated cPARP expression. Further, we demonstrate that the AT2 receptor attenuates NMDA-mediated subunit phosphorylation and current to decrease intracellular Ca2+ levels and subsequent downstream signaling. Taken together these results characterize a novel mechanism for describing the AT2 receptor's neuroprotective functions.","abstract_html":"In the current study, we examined whether treatment with Ang II regulates NMDA-mediated current, signaling and apoptosis. Western blot analysis revealed that Ang II, acting primarily through AT2 receptor activation of the protein phosphatase 2A (PP2A), attenuated NMDA-mediated increases in extracellular regulated kinase-2 (ERK-2) activity. We have identified that AT2 receptor activation inhibits cleavage of the DNA repair enzyme poly-(ADP-ribose) polymerase (PARP) following treatment with NMDA. Inhibition of ERK with MEK inhibitors (PD98059 and U0126) significantly decreased PARP cleavage (cPARP), while inhibition of PP2A with 10 nM okadaic acid, significantly increased NMDA-mediated cPARP expression. Further, we demonstrate that the AT2 receptor attenuates NMDA-mediated subunit phosphorylation and current to decrease intracellular Ca2+ levels and subsequent downstream signaling. Taken together these results characterize a novel mechanism for describing the AT2 receptor's neuroprotective functions.","abstract_has_math":false,"creators":["Andres, Robert Douglas"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Cell and Developmental Biology","degree_department":null,"school":null,"contributors":["Cameron, Jo Ann"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-09-28T15:03:18Z","date_published":"2015-09-28T15:03:18Z","updated_at":"2026-07-22T22:26:27Z","subjects":["Biology, Cell"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(MiAaPQ)AAI3314723"],"render_values":[{"text":"(MiAaPQ)AAI3314723","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/86311","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Cameron, Jo Ann"]},{"key":"dc:creator","label":"Author","values":["Andres, Robert Douglas"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-09-28T15:03:18Z","10000-01-01","2008"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell and Developmental Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology, Cell"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/86311","(MiAaPQ)AAI3314723"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["In the current study, we examined whether treatment with Ang II regulates NMDA-mediated current, signaling and apoptosis. Western blot analysis revealed that Ang II, acting primarily through AT2 receptor activation of the protein phosphatase 2A (PP2A), attenuated NMDA-mediated increases in extracellular regulated kinase-2 (ERK-2) activity. We have identified that AT2 receptor activation inhibits cleavage of the DNA repair enzyme poly-(ADP-ribose) polymerase (PARP) following treatment with NMDA. Inhibition of ERK with MEK inhibitors (PD98059 and U0126) significantly decreased PARP cleavage (cPARP), while inhibition of PP2A with 10 nM okadaic acid, significantly increased NMDA-mediated cPARP expression. Further, we demonstrate that the AT2 receptor attenuates NMDA-mediated subunit phosphorylation and current to decrease intracellular Ca2+ levels and subsequent downstream signaling. Taken together these results characterize a novel mechanism for describing the AT2 receptor's neuroprotective functions.","Made available in DSpace on 2015-09-28T15:03:18Z (GMT). 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Western blot analysis revealed that Ang II, acting primarily through AT2 receptor activation of the protein phosphatase 2A (PP2A), attenuated NMDA-mediated increases in extracellular regulated kinase-2 (ERK-2) activity. We have identified that AT2 receptor activation inhibits cleavage of the DNA repair enzyme poly-(ADP-ribose) polymerase (PARP) following treatment with NMDA. Inhibition of ERK with MEK inhibitors (PD98059 and U0126) significantly decreased PARP cleavage (cPARP), while inhibition of PP2A with 10 nM okadaic acid, significantly increased NMDA-mediated cPARP expression. Further, we demonstrate that the AT2 receptor attenuates NMDA-mediated subunit phosphorylation and current to decrease intracellular Ca2+ levels and subsequent downstream signaling. Taken together these results characterize a novel mechanism for describing the AT2 receptor's neuroprotective functions.","Made available in DSpace on 2015-09-28T15:03:18Z (GMT). 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