Apoptosis of spinal cord neurons by preventing depletion nicotine attenuates arachidonic acid-induced of neurotrophic factors.
Increased levels of free fatty acids and, in particular, arachidonic acid can lead to induction of apoptosis of spinal cord neurons. Because of the importance of neurotrophic factors in cell survival and death, mRNA and protein levels of brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (FGF-2) were studied in cultured spinal cord neurons treated with arachidonic acid. In addition, the present study focused on the effects of nicotine and neuronal nicotinic acetylcholine receptors (nAChRs) on these processes. A 2-h exposure to arachidonic acid markedly diminished expression of BDNF and FGF-2. These effects were fully prevented by pretreatment with 10 microM nicotine. Mecamylamine (a non-specific antagonist of nAChRs) and alpha-bungarotoxin (a specific antagonist of the nAChRalpha7) completely inhibited nicotine-mediated protection against arachidonic acid-induced alterations of BDNF and FGF-2. In addition, nicotine, BDNF and FGF-2 fully protected against arachidonic acid-induced apoptosis of spinal cord neurons. BDNF and FGF-2 were effective in prevention of apoptotic cell death even when applied 2 h after the beginning of arachidonic acid treatment. These results suggest that arachidonic acid can induce apoptosis of spinal cord neurons by depletion of neurotrophic factors and that nicotine can protect against these effects through the nAChRalpha7-mediated pathway.
Garrido
Rosario
R
Department of Surgery, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
Springer
Joe E
JE
Hennig
Bernhard
B
Toborek
Michal
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016718:Arachidonic Acid / Q000633:toxicity; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000187:drug effects; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000187:drug effects; D051379:Mice; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D016222:Fibroblast Growth Factor 2; D016718:Arachidonic Acid; D009538:Nicotine