title: Effects of lipoic acid on antiapoptotic genes in control and ethanol-treated fetal rhombencephalic neurons.
abstract: This laboratory showed that ethanol augments apoptosis in fetal rhombencephalic neurons and co-treatment with alpha-lipoic acid (LA) or one of several other antioxidants prevents ethanol-associated apoptosis. Because ethanol increases oxidative stress, which causes apoptosis, it is likely that some of the neuroprotective effects of LA and other antioxidants involve classical antioxidant actions. Considering the reported link of LA with pro-survival cell signaling, it is also possible that LA's neuroprotective effects involve additional mechanisms. The present study investigated the effects of LA on ethanol-treated fetal rhombencephalic neurons with regard to oxidative stress and up-regulation of the pro-survival genes Xiap and Bcl-2. We included parallel gene expression studies with N-acetyl cysteine (NAC) to determine whether LA's effects on Xiap and Bcl-2 were shared by other antioxidants. We also used enzyme inhibitors to determine which signaling pathway(s) might be involved with the effects of LA. The results of this investigation showed that LA treatment of ethanol-treated neurons exerted several pro-survival effects. LA blocked two pro-apoptotic changes, i.e., the ethanol-associated rise in ROS and caspase-3. LA also up-regulated the expression genes that encode the anti-apoptotic proteins Bcl-2 and Xiap by a mechanism that involves NF-κB. NAC also up-regulated Bcl-2 and Xiap. Thus, the neuroprotective effects of LA and NAC could involve up-regulation of pro-survival genes as well as their classical antioxidant actions.
authors.affiliation: Graduate Program in Cell Biology, Neurobiology, and Anatomy, Loyola University Chicago-Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA.
authors.forename: Angeline M
authors.initials: AM
authors.lastname: Antonio
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Gillespie
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Druse-Manteuffel
mesh_terms: D000438:Alcohols / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects* / Q000235:genetics; D000431:Ethanol / Q000633:toxicity; D005333:Fetus; D015870:Gene Expression / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000187:drug effects*; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000438:Alcohols; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D000431:Ethanol; D008063:Thioctic Acid