tailieunhanh - Báo cáo khoa học: Differential regulation of fatty acid amide hydrolase promoter in human immune cells and neuronal cells by leptin and progesterone

We have shown recently that in human T lymphocytes, leptin stimulates activity and expression of the endocan-nabinoid-degrading enzyme fatty acid amide hydrolase (FAAH), through STAT3 (signal transducer and activator of transcription 3) and its CRE (cAMP response element)-like transcriptional target in the FAAH promoter [Maccar-rone, M., Di Rienzo, M., Finazzi-Agro`,A., &Rossi,A. (2003) J. Biol. Chem. 278, 13318–13324]. We have also shown that progesterone, alone or additively with leptin, up-regulates theFAAHgene in human T-cells, through the Ikaros transcription factor [Maccarrone, M., Bari, M., Di Rienzo,. | Eur. J. Biochem. 271 4666-4676 2004 FEBS 2004 doi Differential regulation of fatty acid amide hydrolase promoter in human immune cells and neuronal cells by leptin and progesterone Mauro Maccarrone1 2 Valeria Gasperi3 Filomena Fezza1 Alessandro Finazzi-Agro3 and Antonello Rossi3 1 Department of Biomedical Sciences University of Teramo Italy 2IRCCS C. Mondino Mondino-Tor Vergata-Santa Lucia Center for Experimental Neurobiology Rome Italy 3Department of Experimental Medicine and Biochemical Sciences University of Rome Tor Vergata Rome Italy We have shown recently that in human T lymphocytes leptin stimulates activity and expression of the endocannabinoid-degrading enzyme fatty acid amide hydrolase FAAH through STAT3 signal transducer and activator of transcription 3 and its CRE cAMP response element -like transcriptional target in the FAAH promoter Maccar-rone M. Di Rienzo M. Finazzi-Agro A. Rossi A. 2003 J. Biol. Chem. 278 13318-13324 . We have also shown that progesterone alone or additively with leptin up-regulates the FAAH gene in human T-cells through the Ikaros transcription factor Maccarrone M. Bari M. Di Rienzo M. Finazzi-Agro A. Rossi A. 2003 J. Biol. Chem. 278 32726-32732 . Here we extend these observations to immortalized human lymphoma U937 cells where stimulation of FAAH by leptin up to w 300 of the controls involves binding to a leptin receptor Kd nM Bmax 382 5 fmol-mg protein-1 appar ent molecular mass of w 110 kDa and stimulation by progesterone involves an intracellular receptor of w 120 kDa. Unlike FAAH the other proteins of the endocannabinoid system are not modulated by the two hormones. Interestingly human neuroblastoma CHP100 cells also have a leptin receptor w 110 kDa Kd nM Bmax 339 8 fmolmg protein-1 a progesterone receptor w 120 kDa STAT3 and Ikaros yet their FAAH is not activated by leptin or progesterone. These data corroborated by transient expression and electrophoretic mobility-shift .