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The role and regulation of protein phosphatase‐1 following oxygen and glucose deprivation in neuroblastoma cells
Author(s) -
Zaydman Anna A,
Yu Jieying,
Hemmings Hugh C.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.954.5
Subject(s) - phosphatase , sh sy5y , protein kinase a , kinase , neuroblastoma , neuroprotection , dephosphorylation , microbiology and biotechnology , phosphorylation , protein phosphatase 2 , cytosol , chemistry , biology , biochemistry , enzyme , cell culture , pharmacology , genetics
Protein phosphatase (PP)‐1 is a major serine/threonine phosphatase that dephosphorylates critical regulators of energy metabolism, ionic balance, and apoptosis. PP‐1 I , an important regulated form of PP‐1, is activated in vivo following cardiac arrest and resuscitation in a clinically relevant pig model of transient global cerebral ischemia/reperfusion. The role of PP‐1 I activation was tested using specific cell‐permeable inhibitors in a neuroblastoma cell (SH‐SY5Y) model of ischemia/reperfusion, oxygen and glucose deprivation (OGD). Activation of PP‐1 I purified from pig brain requires pre‐incubation with Mg 2+ /ATP, consistent with the regulation of PP‐1 I activity by an activating kinase. PP‐1 I purified from control or ischemic pig brain contained PP‐1 catalytic subunit and inhibitor‐2 (I‐2) regulatory subunit as well as PFTAIRE kinase, a novel protein component of PP‐1 I identified by mass spectrometry. We investigated the regulation of PP‐1 I phosphatase activity by PFTAIRE kinase using in vitro PP‐1 I assays together with phosphorylation assay of I‐2. We also investigated the role of PFTAIRE kinase in PP‐1 I activation and cell death following OGD in neuroblastoma cells. These findings implicate PFTAIRE in the ischemic activation of PP‐1 I activity in neuronal cells and suggest inhibition of PP‐1 I as a possible target for neuroprotection in global cerebral ischemia. Supported by NIH grant NS 56315.