ERK 1/2 signaling pathway is involved in nicotine-mediated neuroprotection in spinal cord neurons |
| |
Authors: | Toborek Michal Son Kwang Won Pudelko Anna King-Pospisil Kelley Wylegala Edward Malecki Andrzej |
| |
Institution: | Department of Surgery, University of Kentucky, Lexington, Kentucky 40536, USA. michal.toborek@uky.edu |
| |
Abstract: | 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. |
| |
Keywords: | spinal cord injury nicotine fatty acids apoptosis signal transduction |
本文献已被 PubMed 等数据库收录! |
|