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 defici ts in young children, possibly due to its actions on specific targets in the developing nervous system. Protein glycosylation has been demon strated to play a critical role during CNS development, and the negati vely charged sialic acid group has been particularly associated with t he modulation of cell adhesion. In this study, we have used an in vitr o model system to examine the effect of subchronic low-level lead on t he 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 cellu lar ST activity, the level of induction being more pronounced in embry onically derived cells compared with postnatally derived cells. The in crease was not due to a direct interaction of the metal with the enzym e and was only observed after at least 72 h exposure to the metal. The induction was blocked by the protein synthesis inhibitor, cycloheximi de, and could be reversed upon removal of the metal. The increase was due primarily to the induction of the alpha 2,3(N) ST enzyme with no e ffect on the expression of the alpha 2,6(N) enzyme. These results sugg est that the ST enzyme may serve as a target for the actions of chroni c low-level lead in vivo with an alteration in the developmental regul ation of protein glycosylation being at least partially responsible fo r the behavioral deficits associated with toxin exposure. (C) 1998 Aca demic Press.