Angiotensin Type-2 (At2) Receptor Modulation of Nmda-Mediated Current, Signaling and Apoptosis

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Cell and Developmental Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Andres, Robert Douglas

Contributors dc:contributor

• Cameron, Jo Ann

• Biology, Cell

Language dc:language

eng

Identifier

(MiAaPQ)AAI3314723

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/86311