Document Detail


Tartrate-resistant acid phosphatase: a potential target for therapeutic gold.
MedLine Citation:
PMID:  15338465     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gold compounds are disease-modifying agents for the treatment of rheumatoid arthritis. They act on the immune system but the mechanism is not fully understood. Gold has been shown to affect antigen processing by T-cells and also reduces expression of cytokines in macrophages. Tartrate-resistant acid phosphatase (TRAP), expressed by osteoclasts, macrophages and dendritic cells is an enzyme with roles in skeletal metabolism and the immune response. TRAP is able to degrade skeletal phosphoproteins including osteopontin, identical to the T-cell cytokine, Eta-1; we thus propose that TRAP regulates the Eta-1 pathway common to the immune system and skeleton. We compared the distribution of osteopontin and TRAP in sections of 18-day-old embryonic mice by immunohistochemistry. Both proteins occurred in the same locations. To determine whether gold compounds exert their effects by modification of TRAP activity, we examined the action of gold chloride and the prodrugs, aurothioglucose and aurothiomalate on the dephosphorylation of osteopontin by TRAP. Aurothioglucose and aurothiomalate had little effect on phosphatase activity; gold chloride was a potent non-competitive inhibitor (Ki < 47 x 10(-9) M). These findings indicate a possible molecular mechanism for the action of therapeutic gold and further implicate TRAP in the control of immunity.
Authors:
Alison R Hayman; Timothy M Cox
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell biochemistry and function     Volume:  22     ISSN:  0263-6484     ISO Abbreviation:  Cell Biochem. Funct.     Publication Date:    2004 Sep-Oct
Date Detail:
Created Date:  2004-08-31     Completed Date:  2005-03-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8305874     Medline TA:  Cell Biochem Funct     Country:  England    
Other Details:
Languages:  eng     Pagination:  275-80     Citation Subset:  IM    
Affiliation:
Department of Clinical Veterinary Science, University of Bristol, Bristol, UK. Alison.Hayman@bristol.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Acid Phosphatase / antagonists & inhibitors,  metabolism*
Animals
Antirheumatic Agents / pharmacology
Blotting, Western
Bone and Bones / chemistry,  embryology
Enzyme Inhibitors / pharmacology
Female
Gold Compounds / pharmacology*
Immunohistochemistry
Isoenzymes / antagonists & inhibitors,  metabolism*
Male
Mice
Molybdenum / pharmacology
Osteopontin
Recombinant Proteins / metabolism
Sialoglycoproteins / analysis,  metabolism
Skin / chemistry,  embryology
Vanadates / pharmacology
Chemical
Reg. No./Substance:
0/Antirheumatic Agents; 0/Enzyme Inhibitors; 0/Gold Compounds; 0/Isoenzymes; 0/Recombinant Proteins; 0/Sialoglycoproteins; 0/Spp1 protein, mouse; 0/Vanadates; 106441-73-0/Osteopontin; 11118-27-7/gold chloride; 14259-85-9/molybdate; 7439-98-7/Molybdenum; EC 3.1.3.-/tartrate-resistant acid phosphatase; EC 3.1.3.2/Acid Phosphatase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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