Calcium/Calmodulin-Dependent Protein Kinase II Activity and Expression Are Altered in the Hippocampus of Pb2+- Exposed Rats

Details

• Personal Author:
  Guilarte TR ; O'Callaghan JP ; Toscano CD
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Calcium Compounds Enzymes Laboratories Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Animal-studies Author Keywords: Calcium/Calmodulin Dependent Protein Kinase II (CaMKII) Calcium-compounds Calcium Signaling Enzyme Kinetics Exposure-levels In-vitro-studies In-vivo-studies Laboratory-animals Lead (Pb2+) Nervous-system-disorders Neurotoxic-effects Neurotoxicity Neurotoxins NMDA Receptor (NMDAR) Phosphorylation Proteins

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• ISSN:
  0006-8993
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  51-58
• Volume:
  1044
• Issue:
  1
• NIOSHTIC Number:
  nn:20027079
• Citation:
  Brain Res 2005 May; 1044(1):51-58
• Contact Point Address:
  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
• Email:
  jguilart@jhsph.edu
• CAS Registry Number:
  Calcium (CAS RN 7440-70-2)
• Federal Fiscal Year:
  2005
• Peer Reviewed:
  True
• Source Full Name:
  Brain Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9174044be0195a02079772e01565a40ed260dba0a625dd1368348d6581fa7d0433ac1254c7991613012e28957e6a1b13dd0a4cbc47d6a3e0769321b84fc77260
• Download URL:
  https://stacks.cdc.gov/view/cdc/197451/cdc_197451_DS1.pdf
• File Type:
  [PDF - 225.01 KB ]