Abstract
We have recently reported that leptin (L) and progesterone (P) stimulate the activity and the expression of the endocannabinoid-degrading enzyme anandamide hydrolase (fatty acid amide hydrolase, FAAH) in human lymphoma U937 cells, but not in human neuroblastoma CHP100 cells. We have also shown that leptin and progesterone do not affect the proteins of the endocannabinoid system that synthesize and transport AEA. Here, we have summarized these findings, and have extended them by investigating the effect of leptin and progesterone on the endogenous levels of AEA. We show that leptin and progesterone significantly reduce AEA content in U937 cells (down to ∼20% and ∼50% of the controls, respectively), whereas they are ineffective on AEA levels in CHP100 cells. In addition, we show that leptin and progesterone prevent the pro-apoptotic activity of AEA in U937 cells, reducing DNA fragmentation by ∼50% and ∼35% compared to controls, respectively. Instead, neither hormone affects apoptosis induced by AEA in CHP100 cells. Since the anti-apoptotic activity of leptin and progesterone parallels their effect on FAAH, it can be suggested that enhanced degradation of AEA is the means to protect U937 cells against the toxicity of this compound. Altogether, these data suggest that a cell-specific regulation of FAAH gene might modulate the apoptotic potential of endocannabinoids along the neuroimmune axis. These findings might be relevant for the development of cell-selective drugs targeted towards FAAH.
| Original language | English |
|---|---|
| Pages (from-to) | 811-817 |
| Number of pages | 7 |
| Journal | NeuroToxicology |
| Volume | 26 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Oct 2005 |
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Keywords
- Anandamide
- Apoptosis
- FAAH
- Immune cells
- Leptin
- Neuroimmune axis
- Neurons
- Progesterone
ASJC Scopus subject areas
- Neuroscience(all)
- Cellular and Molecular Neuroscience
- Toxicology
Cite this
Further insights into the regulation of human FAAH by progesterone and leptin : Implications for endogenous levels of anandamide and apoptosis of immune and neuronal cells. / Gasperi, Valeria; Fezza, Filomena; Spagnuolo, Paola; Pasquariello, Nicoletta; MacCarrone, Mauro.
In: NeuroToxicology, Vol. 26, No. 5, 10.2005, p. 811-817.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Further insights into the regulation of human FAAH by progesterone and leptin
T2 - Implications for endogenous levels of anandamide and apoptosis of immune and neuronal cells
AU - Gasperi, Valeria
AU - Fezza, Filomena
AU - Spagnuolo, Paola
AU - Pasquariello, Nicoletta
AU - MacCarrone, Mauro
PY - 2005/10
Y1 - 2005/10
N2 - We have recently reported that leptin (L) and progesterone (P) stimulate the activity and the expression of the endocannabinoid-degrading enzyme anandamide hydrolase (fatty acid amide hydrolase, FAAH) in human lymphoma U937 cells, but not in human neuroblastoma CHP100 cells. We have also shown that leptin and progesterone do not affect the proteins of the endocannabinoid system that synthesize and transport AEA. Here, we have summarized these findings, and have extended them by investigating the effect of leptin and progesterone on the endogenous levels of AEA. We show that leptin and progesterone significantly reduce AEA content in U937 cells (down to ∼20% and ∼50% of the controls, respectively), whereas they are ineffective on AEA levels in CHP100 cells. In addition, we show that leptin and progesterone prevent the pro-apoptotic activity of AEA in U937 cells, reducing DNA fragmentation by ∼50% and ∼35% compared to controls, respectively. Instead, neither hormone affects apoptosis induced by AEA in CHP100 cells. Since the anti-apoptotic activity of leptin and progesterone parallels their effect on FAAH, it can be suggested that enhanced degradation of AEA is the means to protect U937 cells against the toxicity of this compound. Altogether, these data suggest that a cell-specific regulation of FAAH gene might modulate the apoptotic potential of endocannabinoids along the neuroimmune axis. These findings might be relevant for the development of cell-selective drugs targeted towards FAAH.
AB - We have recently reported that leptin (L) and progesterone (P) stimulate the activity and the expression of the endocannabinoid-degrading enzyme anandamide hydrolase (fatty acid amide hydrolase, FAAH) in human lymphoma U937 cells, but not in human neuroblastoma CHP100 cells. We have also shown that leptin and progesterone do not affect the proteins of the endocannabinoid system that synthesize and transport AEA. Here, we have summarized these findings, and have extended them by investigating the effect of leptin and progesterone on the endogenous levels of AEA. We show that leptin and progesterone significantly reduce AEA content in U937 cells (down to ∼20% and ∼50% of the controls, respectively), whereas they are ineffective on AEA levels in CHP100 cells. In addition, we show that leptin and progesterone prevent the pro-apoptotic activity of AEA in U937 cells, reducing DNA fragmentation by ∼50% and ∼35% compared to controls, respectively. Instead, neither hormone affects apoptosis induced by AEA in CHP100 cells. Since the anti-apoptotic activity of leptin and progesterone parallels their effect on FAAH, it can be suggested that enhanced degradation of AEA is the means to protect U937 cells against the toxicity of this compound. Altogether, these data suggest that a cell-specific regulation of FAAH gene might modulate the apoptotic potential of endocannabinoids along the neuroimmune axis. These findings might be relevant for the development of cell-selective drugs targeted towards FAAH.
KW - Anandamide
KW - Apoptosis
KW - FAAH
KW - Immune cells
KW - Leptin
KW - Neuroimmune axis
KW - Neurons
KW - Progesterone
UR - http://www.scopus.com/inward/record.url?scp=26444607495&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=26444607495&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2005.08.002
DO - 10.1016/j.neuro.2005.08.002
M3 - Article
C2 - 16154199
AN - SCOPUS:26444607495
VL - 26
SP - 811
EP - 817
JO - NeuroToxicology
JF - NeuroToxicology
SN - 0161-813X
IS - 5
ER -