ERK 1/2 signaling pathway is involved in nicotine-mediated neuroprotection in spinal cord neurons.
Evidence indicates that agonists of neuronal nicotinic receptors (nAChRs), including nicotine, can induce neuroprotective and anti-apoptotic effects in the CNS. To study these mechanisms, the present study focused on nicotine-mediated modulation of the extracellular regulated kinase 1 and 2 (ERK1/2) pathway in cultured spinal cord neurons. Exposure to nicotine (0.1-10 microM) for as short as 1 min markedly upregulated levels of phosphorylated ERK1/2 (pERK1/2) and increased total ERK1/2 activity. Inhibition studies with mecamylamine and alpha-bungarotoxin revealed that these effects were mediated by the alpha7 nicotinic receptor. In addition, pre-exposure to U0126, a specific inhibitor of the ERK1/2 signaling, prevented nicotine-mediated anti-apoptotic effects. To indicate if treatment with nicotine also can activate ERK1/2 in vivo, a moderate spinal cord injury (SCI) was induced in rats using a weight-drop device and nicotine was injected 2 h post-trauma. Consistent with in vitro data, nicotine increased levels of pERK1/2 in this animal model of spinal cord trauma. Results of the present study indicate that the ERK1/2 pathway is involved in anti-apoptotic effects of nicotine in spinal cord neurons and may be involved in therapeutic effects of nicotine in spinal cord trauma.
Toborek
Michal
M
Department of Surgery, University of Kentucky, Lexington, Kentucky 40536, USA. michal.toborek@uky.edu
Son
Kwang Won
KW
Pudelko
Anna
A
King-Pospisil
Kelley
K
Wylegala
Edward
E
Malecki
Andrzej
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D013119:Spinal Cord Injuries / Q000201:enzymology; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579166:Chrna7 protein, mouse; C579165:Chrna7 protein, rat; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3