Upregulation of Protein Phosphatase 2A and NR3A-Pleiotropic Effect of Simvastatin on Ischemic Stroke Rats |
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| Authors: | Minxia Zhu Jin Wang Min Liu Dongshu Du Chunmei Xia Linlin Shen Danian Zhu |
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| Institution: | 1. Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.; 2. Medical College of Tibet University for Nationalities, Xianyang, Shaanxi, China.; Virginia Commonwealth University, United States of America, |
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| Abstract: | Ca2+ influxes are regulated by the functional state of N-methyl-D-aspartate receptors (NMDARs). Dephosphorylation of NMDARs subunits decreases Ca2+ influxes. NR3, a novel subunit of NMDARs, also decreases Ca2+ influxes by forming new NMDARs with NR1 and NR2. It is meaningful to uncover whether protein phosphatase 2A (PP2A) and NR3A play a role in the protective effect of Simvastatin on ischemic stroke. In the present study, the Sprague-Dawley rats were pretreated with Simvastatin for 7 days before middle cerebral artery occlusion was performed to mimic ischemic stroke. The results showed that Simvastatin decreased brain ischemic infarct area significantly while increasing the expression levels of PP2A and NR3A, thus dephosphorylating the serine sites of NR1 (ser896 and ser897) along with increased enzymatic activities of PP2A. The protein levels of NR3A decreased as the enzymatic activities of PP2A were inhibited by okadaic acid. The results indicated that Simvastatin could protect the cerebrum from ischemic injury through a signaling mechanism involving elevated levels of PP2A and NR3A, and that PP2A might involve in the regulatory mechanism of NR3A expression. |
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