Exposure to lead elevates induction of zif268 and Arc mRNA in rats after electroconvulsive shock: the involvement of protein kinase C.
Exposure to lead is well known to impair cognitive function in young children. Because of the importance of gene regulation for neurodevelopment, we examined the effect of lead on the induction of the mRNA of the immediate early genes zif268 and Arc. The time course for the induction of zif268 mRNA and Arc mRNA by electroconvulsant shock (ECS) was altered in the area of the dentate gyrus of the hippocampus in rats exposed to lead from postnatal days (PND) 1 to 28. Other areas of the hippocampus were not affected by lead. The effects on the induction of zif268 mRNA were observed at blood lead levels as low as 12 microg/dl. No change in the induction of zif268 mRNA was observed in the hippocampus of rats exposed to lead from PND 28 to PND 56. Because of the possible involvement of protein kinase C (PKC) in the effect of lead, activation of different isoforms of PKC was investigated. An increase in the amount of PKC epsilon and PKC gamma was observed at 60 min after ECS in the membrane fraction from hippocampus, indicating activation of these isoforms. The amount of PKC epsilon in membranes was higher in rats exposed to lead than in rats not exposed to lead after ECS. Taken together, the data suggest that lead may disturb regulation of specific immediate early genes by activating PKC epsilon.
Kim
Kyung-Ah
KA
Department of Environmental Health Sciences, School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Chakraborti
Tamal
T
Goldstein
Gary
G
Johnston
Michael
M
Bressler
Joseph
J
D000818:Animals; D015153:Blotting, Western; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1; D004597:Electroshock; D017781:Genes, Immediate-Early / Q000187:drug effects*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000187:drug effects; D007854:Lead / Q000009:adverse effects* / Q000097:blood; D007855:Lead Poisoning / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D011493:Protein Kinase C / Q000032:analysis / Q000187:drug effects*; D051744:Protein Kinase C-epsilon; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis / Q000187:drug effects* / Q000235:genetics
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C092069:activity regulated cytoskeletal-associated protein; D007854:Lead; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon