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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1995-2-21
|
| pubmed:abstractText |
The production of hydrogen peroxide (H2O2) as an essential process for iodide organification is a key reaction in TSH-induced thyroid hormone synthesis. Here we characterize the signal transduction pathway involved in TSH-induced H2O2 production in FRTL-5 thyroid cells. At higher than 1 nM TSH, N6-(L-2-phenylisopropyl)adenosine (PIA), an adenosine receptor agonist having, by itself, no influence on H2O2 generation, potentiated this TSH action, whereas the TSH increase and PIA addition reduced cAMP accumulation. RO 20-1724, a phosphodiesterase inhibitor, amplified the TSH-induced cAMP accumulation, but did not change H2O2 generation in the whole range of TSH used. Ca(2+)-mobilizing agonists, GTP and ATP, also induced H2O2 production without stimulating cAMP accumulation. Chelation of intracellular Ca2+ markedly inhibited the TSH action, but intracellular Ca2+ increases by either thapsigargin or ionomycin mimicking it. All of the findings show the participation of Ca2+, but not cAMP, in the action of TSH. Desensitization of protein kinase-C (PKC) did not influence the receptor-mediated H2O2 production, suggesting the reduced importance of PKC activation compared to Ca2+ signaling to the reaction. A rise in intracellular Ca2+ independent of receptor activation also induced H2O2 production as well as arachidonate release, and both were potentiated by PIA. In addition, inhibitors of phospholipase-A2 and the arachidonate metabolic pathway depressed H2O2 generation, suggesting the participation of an arachidonate cascade in the Ca(2+)-dependent H2O2 production. Lipoxygenase inhibitors depressed the Ca2+ action without influencing arachidonate release, suggesting the involvement of a lipoxygenase product(s) of arachidonate in the Ca(2+)-signaling mechanism. In conclusion, in FRTL-5 cells, TSH-induced H2O2 production is mediated not by cAMP, but by the phospholipase-C/Ca2+ cascade, possibly followed by the Ca(2+)-dependent phospholipase-A2/arachidonate cascade. PIA amplifies TSH-induced H2O2 production at the steps of phospholipase-C and phospholipase-A2 activation in a pertussis toxin-sensitive manner.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylisopropyladenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Thyrotropin,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella
|
| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0013-7227
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
136
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
116-23
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| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:7828520-Adenosine,
pubmed-meshheading:7828520-Animals,
pubmed-meshheading:7828520-Arachidonic Acid,
pubmed-meshheading:7828520-Calcium,
pubmed-meshheading:7828520-Cell Line,
pubmed-meshheading:7828520-Cyclic AMP,
pubmed-meshheading:7828520-Enzyme Activation,
pubmed-meshheading:7828520-GTP-Binding Proteins,
pubmed-meshheading:7828520-Hydrogen Peroxide,
pubmed-meshheading:7828520-Pertussis Toxin,
pubmed-meshheading:7828520-Phenylisopropyladenosine,
pubmed-meshheading:7828520-Phospholipases A,
pubmed-meshheading:7828520-Phospholipases A2,
pubmed-meshheading:7828520-Protein Kinase C,
pubmed-meshheading:7828520-Rats,
pubmed-meshheading:7828520-Signal Transduction,
pubmed-meshheading:7828520-Thyroid Gland,
pubmed-meshheading:7828520-Thyrotropin,
pubmed-meshheading:7828520-Virulence Factors, Bordetella
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Thyrotropin-induced hydrogen peroxide production in FRTL-5 thyroid cells is mediated not by adenosine 3',5'-monophosphate, but by Ca2+ signaling followed by phospholipase-A2 activation and potentiated by an adenosine derivative.
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| pubmed:affiliation |
Department of Physical Biochemistry, Gunma University, Maebashi, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|