Ascorbic acid decreases neutral endopeptidase activity in cultured osteoblastic cells

Neprilysin (NEP) is a plasma membrane-bound peptidase with wide expression in kidney, lung, brain and bone. Decreased NEP activity has been linked to increased growth of some cancer cells, but it is unknown whether its activity is related to growth of cells belonging to the osteoblast lineage. We as...

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Bibliographic Details
Published in:Regulatory peptides 2005-08, Vol.130 (1), p.57-66
Main Authors: Schmid, Christoph, Ghirlanda-Keller, Claudia, Gosteli-Peter, Martina
Format: Article
Language:English
Subjects:
Alkaline Phosphatase - metabolism
Animals
Ascorbic acid
Ascorbic Acid - metabolism
Ascorbic Acid - pharmacology
Biological and medical sciences
Blotting, Northern
Blotting, Western
Calcium - metabolism
Cell Membrane - metabolism
Cell Proliferation
Cells, Cultured - cytology
Dexamethasone - pharmacology
DNA - metabolism
Dose-Response Relationship, Drug
Fundamental and applied biological sciences. Psychology
Growth
Insulin-Like Growth Factor I - pharmacology
NEP
Neprilysin - chemistry
Neprilysin - pharmacology
Osteoblasts
Osteoblasts - cytology
Osteoblasts - metabolism
Peptides - chemistry
Rats
Signal Transduction
Subcellular Fractions
Thiorphan - pharmacology
Thymidine - chemistry
Thymidine - metabolism
Time Factors
Transcriptional Activation
Vertebrates: endocrinology
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Summary:Neprilysin (NEP) is a plasma membrane-bound peptidase with wide expression in kidney, lung, brain and bone. Decreased NEP activity has been linked to increased growth of some cancer cells, but it is unknown whether its activity is related to growth of cells belonging to the osteoblast lineage. We assessed NEP activity in an osteoblastic cell line, PyMS, by cleavage of N-Dansyl- d-Ala-Gly- p-nitro-Phe-Gly to Dansyl- d-Ala-Gly. NEP activity was completely blocked by 1 μM thiorphan. Most agents affecting growth of these cells (e.g. calcium, insulin-like growth factor I and dexamethasone) did not regulate NEP activity. Ascorbic acid (ASA) increased thymidine incorporation into DNA and potentiated the stimulatory effect of IGF I on DNA synthesis, an effect which was attenuated by echistatin. ASA decreased NEP activity in a dose-dependent manner, and decreased Western-detectable NEP protein in plasma membranes. ASA affects both integrin receptor-mediated signalling and the processing of regulatory peptides.
ISSN:0167-0115
1873-1686
DOI:10.1016/j.regpep.2005.03.007