Over-expression of alpha7 nicotinic acetylcholine receptor induces sustained ERK phosphorylation and N-cadherin expression in PC12 cells.
Over-expression of alpha7 nicotinic acetylcholine receptor (alpha7nAChR) in PC12 cells, independent of agonistic stimulation, induces marked neurite outgrowth and high capacity for migration and adherence (differentiation-like transformation), and increases tolerance against cell damage. In the present study, we investigated the effects of alpha7nAChR over-expression and nicotine on ERK phosphorylation and N-cadherin expression by comparing 3 groups of cells: PC12 cells transfected with alpha7 subunit cDNA (alpha7pCMV cells); untransfected PC12 cells exposed to 50 microM nicotine (PC12 cells+nicotine); and PC12 cells transfected with vector only (pCMV cells). alpha7 subunit protein was detected in alpha7pCMV cells at 24 to 72 h after transfection. alpha7pCMV cells exhibited sustained expression of phospho-ERKs (p42 and p44) at 24 to 72 h after transfection, and differentiation-like transformation at 72 h after transfection. PC12 cells+nicotine exhibited transient expression of phospho-ERKs at 48 h after addition of nicotine, but did not exhibit differentiation-like transformation. Neither ERK phosphorylation nor differentiation-like transformation was observed in pCMV cells. Expression of surface N-cadherin increased at 72 h after transfection on alpha7pCMV cells, but did not increase on PC12 cells+nicotine or pCMV cells. These findings suggest that, in PC12 cells, over-expression of alpha7nAChR induces sustained activation of ERK, which probably promotes N-cadherin expression and differentiation-like transformation.
Utsugisawa
Kimiaki
K
Department of Neurology, Iwate Medical University, Uchimaru 19-1, Morioka 020, Japan.
Nagane
Yuriko
Y
Obara
Daiji
D
Tohgi
Hideo
H
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D048429:Cell Size; D005434:Flow Cytometry; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D015820:Cadherins; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D009538:Nicotine; D020928:Mitogen-Activated Protein Kinases