Protein Kinase C Does Not Mediate the Inhibitory Action of Lead on Vitamin D3-Dependent Production of Osteocalcin in Osteoblastic Bone Cells

The level of osteocalcin in serum is lower in lead-intoxicated children than in their normal counterparts. To explain this clinical observation, we investigated the mechanism of action of lead on vitamin D3-dependent osteocalcin production. Lead (5–20 μM) blocked the stimulating effects of vitamin D...

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Bibliographic Details
Published in:Toxicology and applied pharmacology 2002-01, Vol.178 (2), p.109-116
Main Authors: Guity, Partow, McCabe, Michael J., Pitts, David K., Santini, Ronald P., Pounds, Joel G.
Format: Article
Language:English
Subjects:
Alkaline Phosphatase - metabolism
Animals
Blotting, Western
Bone and Bones - cytology
Bone and Bones - drug effects
Bone and Bones - metabolism
Bone Development - drug effects
Bone Neoplasms - enzymology
Bone Neoplasms - metabolism
Cell Fractionation
cell signaling
Cholecalciferol - antagonists & inhibitors
Cholecalciferol - physiology
Electrophoresis, Polyacrylamide Gel
lead
Lead - toxicity
osteoblasts
Osteoblasts - drug effects
Osteoblasts - enzymology
Osteoblasts - metabolism
osteocalcin
Osteocalcin - antagonists & inhibitors
Osteocalcin - biosynthesis
Osteosarcoma - enzymology
Osteosarcoma - metabolism
Parathyroid Hormone - metabolism
protein kinase C
Protein Kinase C - metabolism
Rats
Receptors, Glucocorticoid - drug effects
ROS 17/2.8
Tumor Cells, Cultured
vitamin D3
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Summary:The level of osteocalcin in serum is lower in lead-intoxicated children than in their normal counterparts. To explain this clinical observation, we investigated the mechanism of action of lead on vitamin D3-dependent osteocalcin production. Lead (5–20 μM) blocked the stimulating effects of vitamin D3 on osteocalcin production in cultured rat osteosarcoma cells (ROS 17/2.8). It is often suggested that activation of protein kinase C (PKC) is a critical mediator of the toxic actions of lead. Treatment of ROS cells with Gö6976, an inhibitor of PKC α and β isozymes, produced similar effects as lead on vitamin D3-dependent osteocalcin production, while activation of PKC by phorbol-12-myristate-13-acetate (TPA) did not reverse or mimic this effect of lead. Thus activation of PKC is not consistent with the actions of lead on vitamin D3-dependent osteocalcin production. Measurement of PKC enzyme activity showed that 10 μM lead treatment does not activate or inhibit the activity of PKC in ROS cells. Western blot analysis indicated that lead treatment does not translocate PKC α, β, or ζ from cytosol to membrane. Therefore, we concluded that PKC does not mediate the cellular toxicity of lead on vitamin D3-dependent osteocalcin production.
ISSN:0041-008X
1096-0333
DOI:10.1006/taap.1999.8819