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Parathyroid hormone-related protein (107-139) decreases alkaline phosphatase in osteoblastic osteosarcoma cells UMR 106 by a protein kinase C-dependent pathway.

Abstract
The C-terminal (107-111) region of parathyroid hormone-related protein (PTHrP) appears to inhibit osteoclastic bone resorption, and to affect osteoblastic growth and differentiation. We tested the effect of human PTHrP (107-139) on alkaline phosphatase (ALP) activity in osteoblastic osteosarcoma UMR 106 cells. We found that this C-terminal PTHrP peptide, between 10 nM and 10 fM, inhibited ALP activity in these cells during the log phase of growth. Human PTHrP (1-34) amide and human PTHrP (1-141) were as potent as PTHrP (107-139) in growing UMR 106 cells. This inhibitory effect of 10 nM PTHrP (107-139) on ALP activity was also observed in serum-depleted cells, and in the presence of 10 nM dexamethasone, which increased ALP activity by 40% in these cells. In addition, this effect of PTHrP (107-139) was blunted by 25 nM bisindolylmaleimide I, a protein kinase C inhibitor. These results support a role for the C-terminal region of PTHrP as a modulator of bone formation.
AuthorsA Valín, F de Miguel, A García-Ocaña, P Esbrit
JournalCalcified tissue international (Calcif Tissue Int) Vol. 65 Issue 2 Pg. 148-51 (Aug 1999) ISSN: 0171-967X [Print] United States
PMID10430649 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Enzyme Inhibitors
  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments
  • Proteins
  • parathyroid hormone-related protein (107-139)
  • Protein Kinase C
  • Alkaline Phosphatase
Topics
  • Alkaline Phosphatase (antagonists & inhibitors, metabolism)
  • Animals
  • Bone Neoplasms (enzymology)
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors (pharmacology)
  • Humans
  • Osteoblasts (drug effects, enzymology)
  • Osteosarcoma (enzymology)
  • Parathyroid Hormone (pharmacology)
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments (pharmacology)
  • Protein Kinase C (metabolism)
  • Proteins (pharmacology)
  • Rats
  • Tumor Cells, Cultured (drug effects)

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