Antioxidant neuroprotection against ethanol-induced apoptosis in HN2-5 cells.
Earlier studies from this and other laboratories show that ethanol induces apoptotic death of fetal and neonatal neurons. One mechanism that underlies these effects is the ethanol-associated reduction in the phosphatidylinositol 3' kinase pro-survival pathway. Another mechanism involves the oxidative stress caused by the ethanol-associated increase in reactive oxygen species (ROS). In the present study, we used the murine HN2-5 hippocampal-derived cell line to investigate the effects of ethanol on ROS levels and apoptosis. We also investigated the potential neuroprotective effects of two structurally unrelated antioxidants: N-acetylcysteine (NAC) and melatonin. The results demonstrate that NAC blocked an ethanol-associated increase in ROS. In addition, NAC and melatonin prevented the augmentation of apoptosis in ethanol-treated neurons. Both antioxidants significantly elevated the expression of the anti-apoptotic gene XIAP in ethanol-treated and/or control neurons and melatonin increased Bcl-2 expression in ethanol-treated neurons. Thus, it is possible that the neuroprotective effects of NAC and melatonin involve their ability to augment the expression of one or more anti-apoptotic gene as well as their classical antioxidant actions. Additional studies are needed to establish the effectiveness of these antioxidants to prevent the loss of neurons which accompanies in utero exposure to ethanol.
Sheth
Dhara S
DS
Department of Cell Biology, Neurobiology and Anatomy, Loyola University, Stritch School of Medicine, Maywood, IL 60153, USA.
Tajuddin
Nuzhath F
NF
Druse
Mary J
MJ
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use; D020268:Alcohol-Induced Disorders, Nervous System / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000037:antagonists & inhibitors; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D002492:Central Nervous System Depressants; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D000431:Ethanol; D008550:Melatonin; D000111:Acetylcysteine