Nicotine attenuates arachidonic acid-induced neurotoxicity in cultured spinal cord neurons.
Arachidonic acid release from cellular membranes due to spinal cord trauma may be one of the principal destructive events that can lead to progressive injury to spinal cord tissue. Exposure to arachidonic acid can compromise neuronal survival and viability. Because nicotine is known to be a neuroprotective agent, we propose that it can prevent arachidonic acid-induced neurotoxicity. To study this hypothesis, effects of nicotine on mitochondrial function, cellular energy content and apoptotic cell death were measured in cultured spinal cord neurons treated with arachidonic acid. Nicotine attenuated arachidonic acid-induced compromised cell viability and cellular ATP levels in spinal cord neurons. Nicotine exerted these protective effects when used at the concentration of 10 microM and only after a 2-h pre-treatment before a co-exposure to arachidonic acid. Antagonists of nicotinic receptors, such as alpha-bungarotoxin or mecamylamine, only partially reversed these neuroprotective effects of nicotine. In addition, nicotine prevented arachidonic acid-induced activation of caspase-3 activity and apoptotic cell death. These results indicate that nicotine pre-treatment can exert a protective effect against arachidonic acid-induced injury to spinal cord neurons.
Garrido
R
R
Department of Surgery, Division of Neurosurgery, University of Kentucky Medical Center, Lexington, KY 40536, USA.
Malecki
A
A
Hennig
B
B
Toborek
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors*; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D005731:Ganglionic Stimulants; D016718:Arachidonic Acid; D009538:Nicotine; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D020169:Caspases