Calcium/calmodulin-dependent protein kinase II activity and expression are altered in the hippocampus of Pb2+-exposed rats.
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.
Toscano
Christopher D
CD
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.
O'Callaghan
James P
JP
Guilarte
Tomás R
TR
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000145:classification / Q000378:metabolism*; D002147:Calmodulin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D007854:Lead / Q000097:blood / Q000633:toxicity*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D013997:Time Factors
D002147:Calmodulin; D007854:Lead; D013912:Threonine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases