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ERK 1/2 signaling pathway is involved in nicotine‐mediated neuroprotection in spinal cord neurons
Author(s) -
Toborek Michal,
Son Kwang Won,
Pudelko Anna,
KingPospisil Kelley,
Wylegala Edward,
Malecki Andrzej
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21013
Subject(s) - nicotine , mecamylamine , neuroprotection , mapk/erk pathway , spinal cord , nicotinic agonist , pharmacology , spinal cord injury , medicine , receptor , kinase , chemistry , neuroscience , biology , biochemistry
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 µM) 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 α‐bungarotoxin revealed that these effects were mediated by the α7 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. J. Cell. Biochem. 100: 279–292, 2007. © 2006 Wiley‐Liss, Inc.