Linked Life Data

11201848

Source:http://linkedlifedata.com/resource/pubmed/id/11201848

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2001-1-29
pubmed:abstractText
Carnitine (3-hydroxy-4N-trimethylammoniumbutanoate) is a naturally occurring quaternary amine that is ubiquitous in mammalian tissues (concentrations in the order of mM). Based on limited studies of approximately 40 years ago, carnitine was considered to be a peripheral antagonist of thyroid hormone (TH) action. These interesting observations have not been explored. To study the biologic basis of this effect, we tested the following possibilities in three TH-responsive cell lines: (1) inhibition of TH entry into cells; (2) inhibition of TH entry into the nucleus; (3) inhibition of TH interaction with the isolated nuclei; and (4) facilitated efflux of TH from cells. On a preliminary basis we had verified that these cell lines (human skin fibroblasts, human hepatoma cells HepG2, and mouse neuroblastoma cells NB 41A3) take up 14Ccarnitine; however, there was no 14Ccarnitine uptake into the nuclei. Concentrations of unlabeled carnitine as high as 100 mM did not affect (125I)T3 binding to isolated nuclei or exit of TH from cells, thus excluding possibilities numbered 3 and 4. At 10 mM camitine, (125I)T3 and (125I)T4 whole-cell uptake was inhibited by approximately 20% in fibroblasts and in HepG2, but by approximately 5% in NB 41A3 cells. Inhibition of T3 nuclear uptake was evaluated in HepG2 and NB 41A3 cells. At 10 mM carnitine, inhibition of T3 nuclear uptake was disproportionately higher, namely approximately 25% in neurons and 35% in hepatocytes. At 50 mM carnitine, there was a minimal additional decrease in whole-cell uptake of either hormone but a marked decrease in T3 nuclear uptake. The latter inhibition was approximately 60% in neurons and 70% in hepatocytes. We are aware of no inhibitor of TH uptake that has such a markedly different effect on the nuclear versus whole-cell uptake. Our data are consistent with carnitine being a peripheral antagonist of TH action, and they indicate a site of inhibition at or before the nuclear envelope.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1050-7256
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1043-50
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Carnitine is a naturally occurring inhibitor of thyroid hormone nuclear uptake.
pubmed:affiliation
Cattedra di Endocrinologia, University of Messina, School of Medicine, Italy. s.benvenga@me.nettuno.it
pubmed:publicationType
Journal Article