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Calcium/calmodulin-dependent protein kinase II activity and expression are altered in the hippocampus of Pb2+- exposed rats.

Authors
Toscano-CD; O'Callaghan-JP; Guilarte-TR
Source
Brain Res 2005 May; 1044(1):51-58
NIOSHTIC No.
20027079
Abstract
In the present study, we examined whether calcium/calmodulin-dependent protein kinase II (CaMKII) is affected by chronic developmental Pb2+ exposure. The effects of Pb2+ exposure on rat hippocampal CaMKII were assessed by measuring CaMKII activity, phosphorylation of CaMKII at threonine-286, and CaMKII alpha and beta protein levels. In the hippocampus of Pb2+-exposed 50-day-old rats known to exhibit deficits in hippocampal long-term potentiation (LTP) and spatial learning, there was a marked reduction (41%) in the apparent maximal velocity (Vmax) of CaMKII and a significant increase (22%) in apparent affinity of the enzyme. These Pb2+-induced changes in CaMKII activity could not be explained by changes in enzyme phosphorylation at threonine-286 or sensitivity to calmodulin. In vitro incubation of hippocampal homogenates from control rats, but not from Pb2+-exposed rats, with Pb2+ prior to assay recapitulated the increase in the affinity of the enzyme observed with in vivo exposure to Pb2+. Western blots of cytosolic and membrane fractions from hippocampus showed a significant decrease in the levels of CaMKII-beta but not alpha protein in the cytosolic fraction of Pb2+-exposed rats. These findings indicate effects of developmental Pb2+ exposure on CaMKII, a component of calcium signaling associated with synaptic plasticity, learning, and memory.
Keywords
Calcium-compounds; Laboratory-animals; Animals; Animal-studies; Exposure-levels; Proteins; Enzymes; In-vitro-studies; In-vivo-studies; Neurotoxicity; Neurotoxic-effects; Neurotoxins; Nervous-system-disorders
Contact
Division of Toxicological Sciences, Department of Environmental Health Sciences, The Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
CODEN
BRREAP
CAS No.
7440-70-2
Publication Date
20050517
Document Type
Journal Article
Email Address
jguilart@jhsph.edu
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0006-8993
NIOSH Division
HELD
Source Name
Brain Research
State
WV
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