Developmental lead exposure alters the distribution of protein kinase C activity in the rat hippocampus.
Chronic low-level lead (Pb) exposure in children is known to cause a deficit in learning and memory. In vitro studies have demonstrated that Pb altered protein kinase C (PKC) activity. Especially, hippocampal PKC has been correlated with performance in several learning tasks. The effects of Pb exposure on hippocampal PKC were investigated during development at various postnatal ages: postnatal day (PN) 7, 14, 28, and 56. Two-tenth % Pb acetate was administered to pregnant and lactating dams and then administered to weanling rats in drinking water. PKC activity was measured in both membrane and cytosolic fractions from the hippocampi of the controls and Pb-exposed animals. Pb-induced increase in PKC activity in the cytosolic fraction was observed in the PN56 rats. In contrast, PKC activity was decreased by Pb at PN7 in the membrane fraction. Furthermore, a significant decrease in the ratio of membrane to cytosolic PKC activity which is representative of PKC distribution was observed in the PN28 and PN56 Pb-exposed rats relative to the same-age controls. This study indicates that chronic Pb exposure during development influences hippocampal PKC activity and distribution. These changes may be involved in the subclinical neurotoxicity of chronic Pb exposure in young children.
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216, USA.
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D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D007774:Lactation; D007854:Lead / Q000097:blood / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007854:Lead; D011493:Protein Kinase C