Low level Pb(2+) exposure affects hippocampal protein kinase C gamma gene and protein expression in rats.
We examined the effect of chronic exposure to lead (Pb(2+)) on protein kinase C (PKC) in 50-day-old rat hippocampus. Cytosolic and membrane fractions of hippocampus from Pb(2+)-exposed rats showed reduced expression of PKC gamma protein. In contrast, a significant elevation of PKC gamma mRNA was observed in pyramidal and dentate granule cell layers. Protein expression of alpha, beta I, beta II and epsilon isoenzymes were unchanged in Pb(2+)-exposed rats, as was [(3)H]phorbol 12,13 dibutyrate (PDBu) binding in tissue slices. Differences were not observed in Ca(2+)-dependent or -independent PKC activity, or in PKC-specific back-phosphorylation of hippocampal homogenates from Pb(2+)-exposed rats. Reduced subcellular levels of PKC gamma in Pb(2+)-exposed rats suggest that signal transduction in the hippocampus may be selectively altered and may be important in manifesting Pb(2+)-induced impairments of synaptic plasticity, learning and memory.
Nihei
M K
MK
Department of Environmental Health Sciences, The Johns Hopkins University, School of Hygiene and Public Health, 615 North Wolfe Street, Room W2001, Baltimore, MD 21205, USA.
McGlothan
J L
JL
Toscano
C D
CD
Guilarte
T R
TR
D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology*; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D007854:Lead / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism / Q000494:pharmacology; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011493:Protein Kinase C / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013462:Sulfur Radioisotopes; D014316:Tritium
D002273:Carcinogens; D007527:Isoenzymes; D010761:Phosphorus Radioisotopes; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D014316:Tritium; D007854:Lead; D015240:Phorbol 12,13-Dibutyrate; C087857:protein kinase C gamma; D011493:Protein Kinase C