Abstract
To gain a mechanistic insight into nicotinic receptor-dependent morbidity of tobacco products in the oral cavity, we studied effects of exposures of normal human oral keratinocytes (KCs) for 24 h to environmental tobacco smoke (ETS) vs. equivalent concentration of pure nicotine. The exposed KCs showed a multifold increase of nuclear factor-κB (NF-κB) at the mRNA and protein levels, which could be significantly (p < 0.05) diminished by α-bungarotoxin or transfection with anti-α7 small interfering RNA. An increased protein-binding activity of NF-κB also could be prevented by blocking α7 signaling. The use of pathway inhibitors demonstrated that the Ras/Raf-1/MEK1/ERK steps mediated α7-dependent upregulation of NF-κB. Thus, exposure of KCs to tobacco may lead to the pathobiologic effects via an intracellular signaling pathway downstream of α7 that proceeds through the Ras/Raf-1/MEK1/ERK steps leading to upregulated expression and transactivation of NF-κB.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2191-2194 |
| Number of pages | 4 |
| Journal | Life Sciences |
| Volume | 80 |
| Issue number | 24-25 |
| DOIs | |
| State | Published - May 30 2007 |
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Keywords
- ERK
- Gene expression
- MEK
- NF-κB
- Nicotinic acetylcholine receptors
- Raf
- Ras
ASJC Scopus subject areas
- Pharmacology
Cite this
Receptor-mediated tobacco toxicity : Alterations of the NF-κB expression and activity downstream of α7 nicotinic receptor in oral keratinocytes. / Arredondo, Juan; Chernyavsky, Alexander I.; Jolkovsky, David L.; Pinkerton, Kent E; Grando, Sergei A.
In: Life Sciences, Vol. 80, No. 24-25, 30.05.2007, p. 2191-2194.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Receptor-mediated tobacco toxicity
T2 - Alterations of the NF-κB expression and activity downstream of α7 nicotinic receptor in oral keratinocytes
AU - Arredondo, Juan
AU - Chernyavsky, Alexander I.
AU - Jolkovsky, David L.
AU - Pinkerton, Kent E
AU - Grando, Sergei A.
PY - 2007/5/30
Y1 - 2007/5/30
N2 - To gain a mechanistic insight into nicotinic receptor-dependent morbidity of tobacco products in the oral cavity, we studied effects of exposures of normal human oral keratinocytes (KCs) for 24 h to environmental tobacco smoke (ETS) vs. equivalent concentration of pure nicotine. The exposed KCs showed a multifold increase of nuclear factor-κB (NF-κB) at the mRNA and protein levels, which could be significantly (p < 0.05) diminished by α-bungarotoxin or transfection with anti-α7 small interfering RNA. An increased protein-binding activity of NF-κB also could be prevented by blocking α7 signaling. The use of pathway inhibitors demonstrated that the Ras/Raf-1/MEK1/ERK steps mediated α7-dependent upregulation of NF-κB. Thus, exposure of KCs to tobacco may lead to the pathobiologic effects via an intracellular signaling pathway downstream of α7 that proceeds through the Ras/Raf-1/MEK1/ERK steps leading to upregulated expression and transactivation of NF-κB.
AB - To gain a mechanistic insight into nicotinic receptor-dependent morbidity of tobacco products in the oral cavity, we studied effects of exposures of normal human oral keratinocytes (KCs) for 24 h to environmental tobacco smoke (ETS) vs. equivalent concentration of pure nicotine. The exposed KCs showed a multifold increase of nuclear factor-κB (NF-κB) at the mRNA and protein levels, which could be significantly (p < 0.05) diminished by α-bungarotoxin or transfection with anti-α7 small interfering RNA. An increased protein-binding activity of NF-κB also could be prevented by blocking α7 signaling. The use of pathway inhibitors demonstrated that the Ras/Raf-1/MEK1/ERK steps mediated α7-dependent upregulation of NF-κB. Thus, exposure of KCs to tobacco may lead to the pathobiologic effects via an intracellular signaling pathway downstream of α7 that proceeds through the Ras/Raf-1/MEK1/ERK steps leading to upregulated expression and transactivation of NF-κB.
KW - ERK
KW - Gene expression
KW - MEK
KW - NF-κB
KW - Nicotinic acetylcholine receptors
KW - Raf
KW - Ras
UR - http://www.scopus.com/inward/record.url?scp=34249704581&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249704581&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2007.01.013
DO - 10.1016/j.lfs.2007.01.013
M3 - Article
C2 - 17291542
AN - SCOPUS:34249704581
VL - 80
SP - 2191
EP - 2194
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 24-25
ER -