Stimulation of sialyltransferase by subchronic low-level lead exposure in the developing nervous system. A potential mechanism of teratogen action.
Chronic low-level lead exposure has been associated with mental deficits in young children, possibly due to its actions on specific targets in the developing nervous system. Protein glycosylation has been demonstrated to play a critical role during CNS development, and the negatively charged sialic acid group has been particularly associated with the modulation of cell adhesion. In this study, we have used an in vitro model system to examine the effect of subchronic low-level lead on the expression and activity of the sialyltransferase (ST) enzyme family. Subchronic exposure of neuronal cells to low concentrations of lead (10(-6)-10(-16) M) resulted in up to a 3-fold induction of total cellular ST activity, the level of induction being more pronounced in embryonically derived cells compared with postnatally derived cells. The increase was not due to a direct interaction of the metal with the enzyme and was only observed after at least 72 h exposure to the metal. The induction was blocked by the protein synthesis inhibitor, cycloheximide, and could be reversed upon removal of the metal. The increase was due primarily to the induction of the alpha2,3(N) ST enzyme with no effect on the expression of the alpha2,6(N) enzyme. These results suggest that the ST enzyme may serve as a target for the actions of chronic low-level lead in vivo with an alteration in the developmental regulation of protein glycosylation being at least partially responsible for the behavioral deficits associated with toxin exposure.
Davey
F D
FD
Department of Pharmacology and Neuroscience, University of Dundee, Dundee, DD1 9SY, Scotland, United Kingdom.
Breen
K C
KC
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D002459:Cell Fusion; D003513:Cycloheximide / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000235:genetics; D006031:Glycosylation; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology; D007854:Lead / Q000633:toxicity*; D051379:Mice; D009447:Neuroblastoma; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000096:biosynthesis; D012799:Sialyltransferases / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D015703:Antigens, CD; D011500:Protein Synthesis Inhibitors; D012795:Sialoglycoproteins; D007854:Lead; D003513:Cycloheximide; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase