Effect of hypoxia on protein phosphatase 2A activity, subcellular distribution and expression in cerebral cortex of newborn piglets

Details

Serval ID
serval:BIB_5B0B7EAB2961
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Effect of hypoxia on protein phosphatase 2A activity, subcellular distribution and expression in cerebral cortex of newborn piglets
Journal
Neuroscience
Author(s)
Truttmann  A. C., Ashraf  Q., Mishra  O. P., Delivoria-Papadopoulos  M.
ISSN
0306-4522 (Print)
Publication state
Published
Issued date
2004
Volume
127
Number
2
Pages
355-63
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Abstract
Protein phosphatase (PP) 2A (PP2A), a major serine/threonine phosphatase highly active in the brain, is known to regulate programmed cell death by different mechanisms including downregulation of Ca++/calmodulin-dependent kinase IV (CaMK IV). Previous studies have shown that CaMK IV activity is increased following cerebral hypoxia. In the present study, we tested the hypothesis that PP2A activity and expression in neuronal nuclei are decreased following hypoxia in newborn piglets. PP and PP2A activities were determined in cerebral subcellular fractions spectrophotometrically using a serine phosphopeptide in the presence or absence of microcystine. The activity of CaMK IV in neuronal nuclei was determined by 33P-incorporation into syntide 2 in the presence or absence of either 1 mM EGTA or 0.8 mM CaCl2 and 1 mM calmodulin. The expressions of PP2A and CaMK IV were measured using Western blot. Following hypoxia, nuclear Ca++-dependent kinase IV activity increased two-fold (P<0.001), whereas PP2A and PP activities significantly decreased (P<0.05) in the neuronal nuclei and membranes but not in the cytosol (P=NS). The distribution of the activity of PP2A was 60% in the cytosol, 35% in membranes and 5% in the neuronal nuclei. The expression of PP2A protein showed a 14% increase and for CaMK IV protein a 100% increase during hypoxia. We propose that due to the decreased activity of PP and PP2A following hypoxia in the neuronal nuclei there is a shift in the balance of the phosphorylation/dephosphorylation system toward increased phosphorylated state thereby increasing activity of the nuclear CaMK IV, modulator of programmed cell death. Since there is only slight increase in the PP2A protein expression, we conclude that the changes observed in the activity of PP2A are due to hypoxia-induced modification of the enzyme itself. We also provide evidence that PP2A is a potential regulator of CaMK IV during hypoxia.
Keywords
Animals Animals, Newborn Apoptosis/physiology Ca(2+)-Calmodulin Dependent Protein Kinase/metabolism Cell Compartmentation/physiology Cell Nucleus/enzymology/ultrastructure Cerebral Cortex/*enzymology/pathology/physiopathology Cerebral Infarction/enzymology/pathology/physiopathology Cytosol/enzymology Down-Regulation/physiology Hypoxia, Brain/*enzymology/pathology/physiopathology Intracellular Membranes/enzymology/ultrastructure Nerve Degeneration/enzymology/pathology/physiopathology Neurons/cytology/*enzymology Phosphoprotein Phosphatase/*metabolism Phosphorylation Sus scrofa Up-Regulation/physiology
Pubmed
Web of science
Create date
28/01/2008 13:50
Last modification date
20/08/2019 14:14
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