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 [Maccarrone, 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 approximate to 300% of the controls) involves binding to a leptin receptor (K-d = 2.0 +/- 0.1 nm, B-max = 382 +/- 5 fmol.mg protein(-1), apparent molecular mass of approximate to 110 kDa), and stimulation by progesterone involves an intracellular receptor of approximate to 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 (approximate to 110 kDa, K-d = 2.2 +/- 0.2 n<smallcapitals>m</smallcapitals>, B-max = 339 +/- 8 fmol.mg protein(-1)), a progesterone receptor (approximate to 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 assays, demonstrate an unprecedented cell-specific regulation of the FAAH gene, which has important implications for the control of tone and activity of AEA along the neuroimmune axis.

Maccarrone, M., Gasperi, V., Fezza, F., FINAZZI AGRO', A., Rossi, A. (2004). Differential regulation of fatty acid amide hydrolase promoter in human immune cells and neuronal cells by leptin and progesterone. EUROPEAN JOURNAL OF BIOCHEMISTRY, 271(23-24), 4666-4676 [10.1111/j.1432-1033.2004.04427.x].

Differential regulation of fatty acid amide hydrolase promoter in human immune cells and neuronal cells by leptin and progesterone

GASPERI, VALERIA;FEZZA, FILOMENA;FINAZZI AGRO', ALESSANDRO;ROSSI, ANTONELLO
2004-01-01

Abstract

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 [Maccarrone, 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 approximate to 300% of the controls) involves binding to a leptin receptor (K-d = 2.0 +/- 0.1 nm, B-max = 382 +/- 5 fmol.mg protein(-1), apparent molecular mass of approximate to 110 kDa), and stimulation by progesterone involves an intracellular receptor of approximate to 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 (approximate to 110 kDa, K-d = 2.2 +/- 0.2 nm, B-max = 339 +/- 8 fmol.mg protein(-1)), a progesterone receptor (approximate to 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 assays, demonstrate an unprecedented cell-specific regulation of the FAAH gene, which has important implications for the control of tone and activity of AEA along the neuroimmune axis.
2004
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/10 - BIOCHIMICA
English
Endocannabinoids; Immune system; Leptin; Neurons; Progesterone
Maccarrone, M., Gasperi, V., Fezza, F., FINAZZI AGRO', A., Rossi, A. (2004). Differential regulation of fatty acid amide hydrolase promoter in human immune cells and neuronal cells by leptin and progesterone. EUROPEAN JOURNAL OF BIOCHEMISTRY, 271(23-24), 4666-4676 [10.1111/j.1432-1033.2004.04427.x].
Maccarrone, M; Gasperi, V; Fezza, F; FINAZZI AGRO', A; Rossi, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/25670
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