Bone-specific alkaline phosphatase activity is inhibited by bisphosphonates: role of divalent cations

Bisphosphonates (BPs) are drugs widely used in the treatment of various bone diseases. BPs localize to bone mineral, and their concentration in resorption lacunae could reach almost milimolar levels. Bone alkaline phosphatase (ALP) is a membrane-bound exoenzyme that has been implicated in bone forma...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Vaisman, Diego Natalio, McCarthy, Antonio Desmond, Cortizo, Ana María
Formato: Articulo
Lenguaje:Inglés
Publicado: 2005
Materias:
Ciencias Exactas
Bisphosphonates
bone-specific alkaline phosphatase
magnesium
Zinc
chelation
osteoblasts
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/136002
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-136002
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Bisphosphonates
bone-specific alkaline phosphatase
magnesium
Zinc
chelation
osteoblasts
spellingShingle Ciencias Exactas
Bisphosphonates
bone-specific alkaline phosphatase
magnesium
Zinc
chelation
osteoblasts
Vaisman, Diego Natalio
McCarthy, Antonio Desmond
Cortizo, Ana María
Bone-specific alkaline phosphatase activity is inhibited by bisphosphonates: role of divalent cations
topic_facet Ciencias Exactas
Bisphosphonates
bone-specific alkaline phosphatase
magnesium
Zinc
chelation
osteoblasts
description Bisphosphonates (BPs) are drugs widely used in the treatment of various bone diseases. BPs localize to bone mineral, and their concentration in resorption lacunae could reach almost milimolar levels. Bone alkaline phosphatase (ALP) is a membrane-bound exoenzyme that has been implicated in bone formation and mineralization. In this study, we investigated the possible direct effect of three N-containing BPs (alendronate, pamidronate, and zoledronate) on the specific activity of bone ALP obtained from an extract of UMR106 rat osteosarcoma cells. Enzymatic activity was measured by spectrophotometric detection of p-nitrophenol product and by in situ visualization of ALP bands after an electrophoresis on cellulose acetate gels. Because ALP is a metalloprotein that contains Zn2+ and Mg2+, both of which are necessary for catalytic function, we also evaluated the participation of these divalent cations in the possible effect of BPs on enzymatic activity. All BPs tested were found to dose-dependently inhibit spectrophotometrically measured ALP activity (93–42% of basal) at concentrations of BPs between 10−5; M and 10−4; M, the order of potency being zoledronate ≊ alendronate > pamidronate. However, coincubation with excess Zn2+ or Mg2+ completely abolished this inhibitory effect. Electrophoretic analysis rendered very similar results: namely a decrease in the enzymatic activity of the bone-ALP band by BPs and a reversion of this inhibition by divalent cations. This study shows that N-containing BPs directly inhibit bone-ALP activity, in a concentration range to which this exoenzyme is probably exposed in vivo. In addition, this inhibitory effect is most possibly the result of the chelation of Zn2+ and Mg2+ ions by BPs.
format Articulo
Articulo
author Vaisman, Diego Natalio
McCarthy, Antonio Desmond
Cortizo, Ana María
author_facet Vaisman, Diego Natalio
McCarthy, Antonio Desmond
Cortizo, Ana María
author_sort Vaisman, Diego Natalio
title Bone-specific alkaline phosphatase activity is inhibited by bisphosphonates: role of divalent cations
title_short Bone-specific alkaline phosphatase activity is inhibited by bisphosphonates: role of divalent cations
title_full Bone-specific alkaline phosphatase activity is inhibited by bisphosphonates: role of divalent cations
title_fullStr Bone-specific alkaline phosphatase activity is inhibited by bisphosphonates: role of divalent cations
title_full_unstemmed Bone-specific alkaline phosphatase activity is inhibited by bisphosphonates: role of divalent cations
title_sort bone-specific alkaline phosphatase activity is inhibited by bisphosphonates: role of divalent cations
publishDate 2005
url http://sedici.unlp.edu.ar/handle/10915/136002
work_keys_str_mv AT vaismandiegonatalio bonespecificalkalinephosphataseactivityisinhibitedbybisphosphonatesroleofdivalentcations
AT mccarthyantoniodesmond bonespecificalkalinephosphataseactivityisinhibitedbybisphosphonatesroleofdivalentcations
AT cortizoanamaria bonespecificalkalinephosphataseactivityisinhibitedbybisphosphonatesroleofdivalentcations
bdutipo_str Repositorios
_version_ 1764820455977385984

Ejemplares similares