Modulation of developmental cerebellar ornithine decarboxylase activity by lead-acetate.
The developing brain is particularly susceptible to the neurotoxic effects of lead exposure. The ontological profile of ornithine decarboxylase (ODC) activity in the cerebellum was examined following lactational exposure of rats to 0.2% lead acetate (Pb). Relative to controls, Pb-exposure induced ODC activity levels in a transient manner with a 50% increase at postnatal day (PND) 6, a 20% increase at PND 9, returning to control basal levels by PND 15. These effects were seen at exposure levels of Pb that did not alter the normal growth and body weight of either the lactating dam or the developing pups. Basal cerebellar ODC activity in homogenates was increased with addition of low concentrations of Pb acetate (0.01 microM and 0.1 microM), while concentrations of 1 microM or greater were inhibitory. The effects of Pb acetate on tissue ODC activity in vitro were not mimicked by the addition of calcium chloride. Unlike tissue ODC activity, incubation of these metals with a pure ODC protein preparation exhibited fluctuations in ODC activity possibly due to the ionic interactions of Pb or calcium chloride. Calcium homeostatic mechanisms appeared to be unchanged with Pb exposure, at this dose, in that neither 45Ca-uptake (both mitochondrial and microsomal) nor synaptosomal Ca(2+)-ATPase activity was altered. These data suggest that alterations in ODC activity may be indicative of subtle toxicant induced perturbations during early development. Although the precise mechanism by which Pb may induce ODC activity in developing tissue is unknown, our results suggest that Pb may specifically alter ODC activity via cytosolic interactions.
Zawia
N H
NH
Lab of Integrated Biology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27707, USA.
Evers
L B
LB
Kodavanti
P R
PR
Harry
G J
GJ
D000367:Age Factors; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002531:Cerebellum; D004305:Dose-Response Relationship, Drug; D007854:Lead / Q000633:toxicity*; D008928:Mitochondria / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000187:drug effects*; D051381:Rats
D007854:Lead; D009955:Ornithine Decarboxylase; D002118:Calcium