Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.99.7 (sialyltransferase)
 1,534 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neural cell adhesion molecule N-CAM is believed to be intimately involved in the structuring of the central nervous system. During post-natal development the molecule exists in 2 forms--a sialic acid-rich form which is preferentially expressed during cell acquisition and fibre outgrowth and a sialic acid-poor form which appears at times coincident with synaptogenesis. The developmental changes between these 2 forms have been demonstrated to be impaired by chronic low-level lead exposure and this is consistent with the reduced synaptic elaboration associated with this action. Here is described the effect of lead on the Golgi-associated sialyltransferase which regulates N-CAM sialylation state. Lead chloride was found to markedly stimulate sialyltransferase with an ED50 of 5 X 10(-7) M in adult Golgi fractions. This was not observed in fractions derived from 12-day old animals. At the concentration of 5 X 10(-5) M lead was found to have a differential effect on the developmental expression of this enzyme. During the early phases of development (days 4-16) sialyltransferase activity was inhibited. However, in coincidence with periods of N-CAM desialylation (days 16-30), it was significantly stimulated. These findings are related to the perturbations of N-CAM function during chronic low-level lead exposure.
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PMID:Lead stimulates Golgi sialyltransferase at times coincident with the embryonic to adult conversion of the neural cell adhesion molecule (N-CAM). 337 25

Neurobehavioral testing of herring gull chicks (Larus argentatus) in both laboratory and field studies indicates that lead exposure during critical periods of development causes neurological deficits that may compromise survival in the wild. Accumulating evidence suggests that lead impairs neurodevelopment, in part, by altering the expression of cell adhesion molecules (CAMs) responsible for the proper formation and maintenance of neural structure and synaptic function. We examined the adhesion molecules NCAM, L1, and N-cadherin in gull brains to determine whether these CAMs are altered by lead exposure and might serve as markers of developmental neurotoxicity. One-day-old chicks were collected from nesting colonies and were laboratory housed. On post-hatching day (PHD) 2, chicks were given 100 mg/kg lead acetate or saline (intraperitoneally). Birds were killed on PHD 34, 44, or 55 (blood-lead levels averaged 27.4, 20.8, and 19.5 microg/dl, respectively). Brains were removed and stored at -70 degrees C until analysis. Expression of CAMs was determined in synaptosomal preparations by Western blotting and the activity of NCAM-associated sialyltransferase (ST) was determined in purified whole brain golgi apparatus. Elevation in synaptosomal polysialylated NCAM expression and a significant increase in golgi ST activity was observed in lead-treated animals at PHD 34. Reductions in synaptosomal N-cadherin were observed at PHD 34 and 44, while L1 expression appeared unaffected by lead at any time-point. By 55 days post-hatching, no differences in N-cadherin expression, polysialylated NCAM expression or NCAM-associated ST activity were seen in lead-treated animals as compared with age-matched control animals. Lead-induced disruption of CAM expression during early neurodevelopment may contribute to behavioral deficits observed in herring gulls in both the laboratory and the field, and may serve as a marker for heavy metal exposure during postnatal development.
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PMID:Developmental lead exposure disturbs expression of synaptic neural cell adhesion molecules in herring gull brains. 1081 46