The effects of ethanol and the serotonin(1A) agonist ipsapirone on the expression of the serotonin(1A) receptor and several antiapoptotic proteins in fetal rhombencephalic neurons.
Previously, this laboratory demonstrated that ethanol reduces the number of developing serotonin (5-HT)-containing neurons by increasing apoptosis. We also found that 5-HT(1A) agonists attenuate the proapoptotic effects of ethanol and the ethanol-mediated reduction of fetal 5-HT neurons. These neuroprotective effects are mediated in part by the ability of 5-HT(1A) agonists to activate the phosphatidyl 3'-kinase (PI-3K) prosurvival pathway. NF-kappaB is one of the downstream effectors activated by this pathway. In the present study, we used quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to determine the effects of 50mM ethanol and 100nM of ipsapirone, a 5-HT(1A) agonist, on the expression of several NF-kappaB-dependent antiapoptotic genes: X-linked inhibitor of apoptosis protein (XIAP), cIAP1, cIAP2, Bcl-2, and Bcl-xl. We also investigated the effects of ethanol and ipsapirone on the expression of the gene encoding the 5-HT(1A) receptor. The results demonstrate that ethanol reduces the expression of several prosurvival genes: XIAP, cIAP1, cIAP2, Bcl-2, and Bcl-xl. Importantly, the ethanol-mediated reduction in the expression of XIAP and Bcl-xl was prevented by co-treatment with ipsapirone. Thus, the damaging effects of ethanol are likely to involve a reduction in several prosurvival proteins. Moreover, the protective effects of ipsapirone on ethanol-treated neurons might involve their ability to prevent the reduction of XIAP and Bcl-xl. Although ipsapirone treatment decreased the expression of cIAP1, Bcl-2, and Bcl-xl in control neurons, our prior studies suggest that their survival is not reduced by ipsapirone. We also observed an increased expression of the 5-HT(1A) receptor in ipsapirone-treated control neurons.
Druse
Mary J
MJ
Division of Molecular and Cellular Biochemistry, Loyola University Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA. mmanteu@lumc.edu
Tajuddin
Nuzhath F
NF
Gillespie
Roberta A
RA
Le
Phong
P