PMID- 12824292
OWN - NLM
STAT- MEDLINE
DCOM- 20030811
LR  - 20151119
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 17
IP  - 11
DP  - 2003 Aug
TI  - L-carnitine: A nutritional modulator of glucocorticoid receptor functions.
PG  - 1553-5
AB  - 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-alpha (GRalpha) functions. Millimolar 
      concentrations of L-carnitine, which were not cytotoxic in vitro, significantly 
      reduced the whole cell binding of [3H]dexamethasone to GRalpha 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 GRalpha 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 GRalpha by the cell. 
      Finally, similarly to glucocorticoids, L-carnitine suppressed tumor necrosis 
      factor-alpha (TNFalpha) and interleukin-12 release by human primary monocytes 
      stimulated with lipopolysaccharide ex vivo. Both GRalpha transactivation and 
      cytokine suppression by L-carnitine were abrogated by the GRalpha-antagonist RU 
      486. Taken together, our results suggest that pharmacological doses of 
      L-carnitine can activate GRalpha and, through this mechanism, regulate 
      glucocorticoid-responsive genes, potentially sharing some of the biological and 
      therapeutic properties of glucocorticoids.
FAU - Alesci, Salvatore
AU  - Alesci S
AD  - Pediatric and Reproductive Endocrinology Branch, National Institute of Child 
      Health and Human Development, National Institutes of Health, Bethesda, Maryland 
      20892-1583, USA. alescis@mail.nih.gov
FAU - De Martino, Massimo U
AU  - De Martino MU
FAU - Mirani, Marco
AU  - Mirani M
FAU - Benvenga, Salvatore
AU  - Benvenga S
FAU - Trimarchi, Francesco
AU  - Trimarchi F
FAU - Kino, Tomoshige
AU  - Kino T
FAU - Chrousos, George P
AU  - Chrousos GP
LA  - eng
PT  - Journal Article
DEP - 20030617
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (glucocorticoid receptor alpha)
RN  - 187348-17-0 (Interleukin-12)
RN  - S7UI8SM58A (Carnitine)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Carnitine/metabolism/*pharmacology
MH  - Cell Nucleus/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Interleukin-12/biosynthesis
MH  - Models, Biological
MH  - Monocytes/drug effects/immunology
MH  - Receptors, Glucocorticoid/*metabolism/physiology
MH  - Transcriptional Activation
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2003/06/26 05:00
MHDA- 2003/08/12 05:00
CRDT- 2003/06/26 05:00
PHST- 2003/06/26 05:00 [pubmed]
PHST- 2003/08/12 05:00 [medline]
PHST- 2003/06/26 05:00 [entrez]
AID - 02-1024fje [pii]
AID - 10.1096/fj.02-1024fje [doi]
PST - ppublish
SO  - FASEB J. 2003 Aug;17(11):1553-5. doi: 10.1096/fj.02-1024fje. Epub 2003 Jun 17.