Premium
l ‐Carnitine: a nutritional modulator of glucocorticoid receptor functions
Author(s) -
Alesci Salvatore,
De Martino Massimo U.,
Mirani Marco,
Benvenga Salvatore,
Trimarchi Francesco,
Kino Tomoshige,
Chrousos George P.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-1024fje
Subject(s) - glucocorticoid receptor , carnitine , glucocorticoid , biology , transactivation , endocrinology , medicine , transcription factor , biochemistry , gene
l ‐Carnitine is an essential nutrient with a major role in cellular energy production. There is evidence that, at high doses, l ‐carnitine might mimic some of the biological activities of glucocorticoids, especially immunomodulation. To explore the molecular basis of this effect, we tested the influence of l ‐carnitine on glucocorticoid receptor‐α (GRα) functions. Millimolar concentrations of l ‐carnitine, which were not cytotoxic in vitro, significantly reduced the whole cell binding of [ 3 H]dexamethasone to GRα by decreasing the affinity of this receptor for its steroid ligand. At the same concentrations, l ‐carnitine was able to trigger nuclear translocation of green fluorescent protein (GFP)‐fused human GRα and transactivate the glucocorticoid‐responsive mouse mammary tumor virus (MMTV) and TAT3 promoters in a dose‐dependent fashion. This effect was solely dependent on the presence of glucocorticoid‐responsive elements on the promoter and on the expression of functional GRα by the cell. Finally, similarly to glucocorticoids, l ‐carnitine suppressed tumor necrosis factor‐α (TNFα) and interleukin‐12 release by human primary monocytes stimulated with lipopolysaccharide ex vivo. Both GRα transactivation and cytokine suppression by l ‐carnitine were abrogated by the GRα‐antagonist RU 486. Taken together, our results suggest that pharmacological doses of l ‐carnitine can activate GRα and, through this mechanism, regulate glucocorticoid‐responsive genes, potentially sharing some of the biological and therapeutic properties of glucocorticoids.