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Calcium/calmodulin-dependent protein kinase II activity and expression are altered in the hippocampus of Pb2+- exposed rats.
Toscano CD; O'Callaghan JP; Guilarte TR
Brain Res 2005 May; 1044(1):51-58
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.
Calcium-compounds; Laboratory-animals; Animals; Animal-studies; Exposure-levels; Proteins; Enzymes; In-vitro-studies; In-vivo-studies; Neurotoxicity; Neurotoxic-effects; Neurotoxins; Nervous-system-disorders; Author Keywords: Calcium/calmodulin dependent protein kinase II (CaMKII); NMDA receptor (NMDAR); Lead (Pb2+); Calcium signaling; Enzyme kinetics; Phosphorylation
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
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