Nicotine upregulates nerve growth factor expression and prevents apoptosis of cultured spinal cord neurons.
Modulation of neurotrophic factor expression may constitute an important part of neuroprotective effects of nicotine. Therefore, the effects of nicotine on expression of nerve growth factor (NGF) and its receptor, tyrosine receptor kinase A (trkA), were studied in cultured spinal cord neurons treated with arachidonic acid. Because injury to spinal cord is associated with elevated levels of arachidonic acid, this cell culture system has been developed in our laboratory as an in vitro model of neuronal injury in spinal cord trauma. Treatment with nicotine markedly upregulated NGF mRNA and protein expression in spinal cord neurons. In addition, a 12h treatment with nicotine increased mRNA levels of trkA. Both nicotine and exogenous NGF inhibited arachidonic acid induced apoptosis of spinal cord neurons. However, the blockage of the trkA receptor prevented nicotine-mediated anti-apoptotic effects. The present results indicate that increased expression of NGF may be an important element of the neuroprotective effects of nicotine in injured spinal cord neurons.
Department of Surgery, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA.
Rosario
R
Garrido
Kelley
K
King-Pospisil
Kwang Won
KW
Son
Bernhard
B
Hennig
Michal
M
Toborek
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D009538:Nicotine; D020932:Nerve Growth Factor; D020917:Receptor, trkA