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|Title:||Angiotensin Type-2 (At2) Receptor Modulation of Nmda-Mediated Current, Signaling and Apoptosis|
|Author(s):||Andres, Robert Douglas|
|Doctoral Committee Chair(s):||Cameron, Jo Ann|
|Department / Program:||Cell and Developmental Biology|
|Discipline:||Cell and Developmental Biology|
|Degree Granting Institution:||University of Illinois at Urbana-Champaign|
|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.|
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008.
|Date Available in IDEALS:||2015-09-28|
This item appears in the following Collection(s)
Dissertations and Theses - Cell and Developmental Biology
Graduate Dissertations and Theses at Illinois
Graduate Theses and Dissertations at Illinois