title: Effects of ethanol and ipsapirone on the expression of genes encoding anti-apoptotic proteins and an antioxidant enzyme in ethanol-treated neurons.
abstract: Previously, this laboratory found that apoptosis was augmented significantly in fetal rhombencephalic neurons when they were treated with 50 mM ethanol for 24 h. These changes were associated temporally with a reduction in the phosphatidylinositol 3-kinase (PI3K) pro-survival pathway and in the downstream expression of several NF-kappaB dependent anti-apoptotic genes. The serotonin-1A agonist ipsapirone prevented ethanol-associated apoptosis; it also activated the PI3K-->pAkt pro-survival pathway and the expression of specific NF-kappaB dependent anti-apoptotic genes in ethanol-treated neurons. The present study investigated the temporal effects of both ethanol and ipsapirone on the expression of three NF-kappaB dependent genes, XIAP, Bcl-XL and catalase; these genes encode proteins that could potentially attenuate ethanol-induced apoptosis. Catalase activity was also measured. All three genes demonstrated an early activation by ethanol. After a brief treatment with 50 mM ethanol, i.e., 2 to 8 h depending on the gene, the expression of XIAP, Bcl-XL, and catalase was significantly increased, possibly as an initial attempt to survive. An ethanol-associated increase in catalase was followed by a rise in catalase activity. However, when ethanol treatment was continued for a longer time, there was a significant reduction in both XIAP and Bcl-XL. In addition, both catalase expression and activity returned to levels found in unstressed controls. Importantly, treatment with ipsapirone augmented the activity of catalase and the expression of Bcl-XL, XIAP, and catalase in ethanol-treated neurons at later time points. The latter effects are likely to contribute to the pro-survival effects of ipsapirone.
authors.affiliation: Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Nuzhath F
authors.initials: NF
authors.lastname: Tajuddin
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Druse
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D000431:Ethanol / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*; D051020:bcl-X Protein / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D011743:Pyrimidines; D051636:X-Linked Inhibitor of Apoptosis Protein; D051020:bcl-X Protein; D000431:Ethanol; C043077:ipsapirone; D002374:Catalase