Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-12-16
pubmed:abstractText
Calciotropic hormones such as parathyroid hormone (PTH) and calcitonin have been shown to have stimulatory and inhibitory effects respectively on superoxide anion (O2-) generation by osteoclasts, but the exact intracellular signalling mediating these pathways has not been investigated. In order to elucidate the intracellular pathways controlling O2- generation, we have carried out a systematic study of the effect of different agents on O2- production in osteoclasts cultured on bovine cortical bone. Dibutyryl cAMP and cholera toxin, while having no effect on the basal level of O2- production in bone-resorbing osteoclasts, were, however, found to completely block the stimulation of free radical production by PTH, pertussis toxin and ionomycin. The stimulation of O2- production was found to be independent of protein kinase C-dependent pathways since the presence of bisindolylmaleimide (GF109203X) (1 microM) did not block stimulation by PTH and pertussis toxin. Interestingly, while exposure to bisindolylmaleimide at this concentration did not have any effect on the basal level of O2- production, exposure to a higher concentration (10 microM), which is known to inhibit both protein kinase C and A, produced significant stimulation. These in vitro findings suggest that in the bone-resorbing cells, cAMP-dependent protein kinases prevent further stimulation of NADPH oxidase by agents such as PTH and pertussis toxin. The increase in cAMP has also been recently demonstrated to be associated with down-regulation of the oxidative burst in adherent neutrophils; and the findings reported here suggest a similar role for cAMP in O2- generation in osteoclasts cultured on bone.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Bucladesine, http://linkedlifedata.com/resource/pubmed/chemical/Cholera Toxin, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Indoles, http://linkedlifedata.com/resource/pubmed/chemical/Ionomycin, http://linkedlifedata.com/resource/pubmed/chemical/Maleimides, http://linkedlifedata.com/resource/pubmed/chemical/Parathyroid Hormone, http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Superoxides, http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella, http://linkedlifedata.com/resource/pubmed/chemical/bisindolylmaleimide I
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-0795
pubmed:author
pubmed:issnType
Print
pubmed:volume
158
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
311-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9846160-Animals, pubmed-meshheading:9846160-Bone Resorption, pubmed-meshheading:9846160-Bucladesine, pubmed-meshheading:9846160-Cells, Cultured, pubmed-meshheading:9846160-Cholera Toxin, pubmed-meshheading:9846160-Cyclic AMP, pubmed-meshheading:9846160-Dose-Response Relationship, Drug, pubmed-meshheading:9846160-Electrochemistry, pubmed-meshheading:9846160-Enzyme Inhibitors, pubmed-meshheading:9846160-Humans, pubmed-meshheading:9846160-Indoles, pubmed-meshheading:9846160-Ionomycin, pubmed-meshheading:9846160-Maleimides, pubmed-meshheading:9846160-Osteoclasts, pubmed-meshheading:9846160-Parathyroid Hormone, pubmed-meshheading:9846160-Pertussis Toxin, pubmed-meshheading:9846160-Protein Kinase C, pubmed-meshheading:9846160-Rats, pubmed-meshheading:9846160-Rats, Wistar, pubmed-meshheading:9846160-Second Messenger Systems, pubmed-meshheading:9846160-Stimulation, Chemical, pubmed-meshheading:9846160-Superoxides, pubmed-meshheading:9846160-Virulence Factors, Bordetella
pubmed:year
1998
pubmed:articleTitle
cAMP-dependent inhibition is dominant in regulating superoxide production in the bone-resorbing osteoclasts.
pubmed:affiliation
Department of Clinical Biochemistry, Medical School, University of Newcastle, UK.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.