PMID- 24358207
OWN - NLM
STAT- MEDLINE
DCOM- 20141021
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 12
DP  - 2013
TI  - Nicotine-induced expression of low-density lipoprotein receptor in oral 
      epithelial cells.
PG  - e82563
LID - 10.1371/journal.pone.0082563 [doi]
LID - e82563
AB  - BACKGROUND: Nicotine use is one of the most important risk factors for the 
      development of cardiovascular and periodontal diseases. Numerous reports have 
      suggested the possible contribution of disturbed lipid metabolism for the 
      development of both disease groups. Despite these observations, little is known 
      about the relationship between tobacco smoking and the development of these 
      diseases. Our previous microarray data revealed that nicotine induced low-density 
      lipoprotein receptor (LDLR) expression in oral epithelial cells (OECs). The aim 
      of the present study was to confirm nicotine-mediated LDLR induction and to 
      elucidate the signaling mechanisms leading to the augmented expression of LDLR in 
      OECs. METHODS AND RESULTS: LDLR and nicotinic acetylcholine receptor (nAChR) 
      subunit expression was detected by real-time PCR. The production of LDLR was 
      demonstrated by immunofluorescence staining. nAChR-mediated LDLR induction was 
      examined by pre-incubation of the cells with its specific inhibitor, 
      alpha-bungarotoxin (alpha-BTX). The functional importance of transcription factor 
      specific protein 1 (Sp1) was examined by luciferase assay, mithramycin 
      pre-incubation or by small interfering RNA (siRNA) transfection. The specific 
      binding of Sp1 to R3 region of LDLR 5'-untranslated region was demonstrated with 
      electrophoretic mobility shift assay (EMSA) and streptavidin-agarose 
      precipitation assay followed by western blotting. The results confirmed that 
      nicotine induced LDLR expression at the transcriptional level. Nicotine was 
      sensed by nAChR and the signal was transduced by Sp1 which bound to the R3 region 
      of LDLR gene. Augmented production of LDLR in the gingival epithelial cells was 
      further demonstrated by immunofluorescence staining using the gingival tissues 
      obtained from the smoking patients. CONCLUSIONS: Taken together, the results 
      suggested that nicotine might contribute to the development of both 
      cardiovascular and periodontal diseases by inducing the LDLR in OECs thereby 
      disturbing lipid metabolism.
FAU - Ito, Satoshi
AU  - Ito S
AD  - Division of Applied Oral Sciences, Nihon University Graduate School of Dentistry, 
      Tokyo, Japan.
FAU - Gojoubori, Takahiro
AU  - Gojoubori T
AD  - Division of Applied Oral Sciences, Nihon University Graduate School of Dentistry, 
      Tokyo, Japan.
FAU - Tsunoda, Kou
AU  - Tsunoda K
AD  - Division of Applied Oral Sciences, Nihon University Graduate School of Dentistry, 
      Tokyo, Japan.
FAU - Yamaguchi, Yoko
AU  - Yamaguchi Y
AD  - Department of Biochemistry, Nihon University School of Dentistry, Tokyo, Japan ; 
      Division of Functional Morphology, Nihon University School of Dentistry, Tokyo, 
      Japan.
FAU - Asano, Masatake
AU  - Asano M
AD  - Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan ; 
      Division of Immunology and Pathobiology, Nihon University School of Dentistry, 
      Tokyo, Japan.
FAU - Goke, Eiji
AU  - Goke E
AD  - Department of Periodontology, Nihon University School of Dentistry, Tokyo, Japan.
FAU - Koshi, Ryosuke
AU  - Koshi R
AD  - Department of Periodontology, Nihon University School of Dentistry, Tokyo, Japan 
      ; Division of Advanced Dental Treatment, Nihon University School of Dentistry, 
      Tokyo, Japan.
FAU - Sugano, Naoyuki
AU  - Sugano N
AD  - Department of Periodontology, Nihon University School of Dentistry, Tokyo, Japan 
      ; Division of Advanced Dental Treatment, Nihon University School of Dentistry, 
      Tokyo, Japan.
FAU - Yoshinuma, Naoto
AU  - Yoshinuma N
AD  - Department of Periodontology, Nihon University School of Dentistry, Tokyo, Japan 
      ; Division of Advanced Dental Treatment, Nihon University School of Dentistry, 
      Tokyo, Japan.
FAU - Komiyama, Kazuo
AU  - Komiyama K
AD  - Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan ; 
      Division of Immunology and Pathobiology, Nihon University School of Dentistry, 
      Tokyo, Japan.
FAU - Ito, Koichi
AU  - Ito K
AD  - Nihon University School of Dentistry, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131216
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Receptors, LDL)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cell Line, Tumor
MH  - Dose-Response Relationship, Drug
MH  - Epithelial Cells/*drug effects/metabolism
MH  - Female
MH  - Humans
MH  - Lipid Metabolism/drug effects/genetics
MH  - Male
MH  - Middle Aged
MH  - Mouth Mucosa/*drug effects/metabolism
MH  - Nicotine/*pharmacology
MH  - Receptors, LDL/*genetics/metabolism
MH  - Up-Regulation/drug effects/genetics
PMC - PMC3864957
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/12/21 06:00
MHDA- 2014/10/22 06:00
PMCR- 2013/12/16
CRDT- 2013/12/21 06:00
PHST- 2013/07/20 00:00 [received]
PHST- 2013/10/25 00:00 [accepted]
PHST- 2013/12/21 06:00 [entrez]
PHST- 2013/12/21 06:00 [pubmed]
PHST- 2014/10/22 06:00 [medline]
PHST- 2013/12/16 00:00 [pmc-release]
AID - PONE-D-13-29680 [pii]
AID - 10.1371/journal.pone.0082563 [doi]
PST - epublish
SO  - PLoS One. 2013 Dec 16;8(12):e82563. doi: 10.1371/journal.pone.0082563. 
      eCollection 2013.