Advanced

Chronic ethanol exposure enhances activating protein-1 transcriptional activity in human neuroblastoma cells

Fried, Ulrik LU ; Kotarsky, Knut LU and Alling, Christer LU (2001) In Alcohol 24(3). p.189-195
Abstract
This study demonstrates a method for studying the effects of ethanol on transcription mediated by activating protein-1 (AP-1). The effects of ethanol on AP-1 activity and on the signaling cascades in this process were investigated by using a reporter gene technique with secreted alkaline phosphatase as the reporter gene coupled to nine DNA AP-1-binding elements. Long-term ethanol exposure (48-72 h) dose dependently enhanced AP-1 transcriptional activity in SH-SY5Y cells. Shorter exposure periods with ethanol did not influence AP-1 transcriptional activity compared with findings for control cells. Inhibition of protein kinase C (PKC) dramatically decreased AP-1 activity in both control and ethanol-exposed cells and abolished the ethanol... (More)
This study demonstrates a method for studying the effects of ethanol on transcription mediated by activating protein-1 (AP-1). The effects of ethanol on AP-1 activity and on the signaling cascades in this process were investigated by using a reporter gene technique with secreted alkaline phosphatase as the reporter gene coupled to nine DNA AP-1-binding elements. Long-term ethanol exposure (48-72 h) dose dependently enhanced AP-1 transcriptional activity in SH-SY5Y cells. Shorter exposure periods with ethanol did not influence AP-1 transcriptional activity compared with findings for control cells. Inhibition of protein kinase C (PKC) dramatically decreased AP-1 activity in both control and ethanol-exposed cells and abolished the ethanol enhancement. This finding suggests a pivotal role for PKC-coupled signaling in AP-1 transcriptional activity. Phorbol ester stimulation of AP-1 transcriptional activity was not influenced by long-term ethanol exposure. This finding indicates that signaling events upstream of PKC are the targets for ethanol. Mitogen-activated protein kinases ERK and p38 may play a role in ethanol-enhanced AP-1 activity because inhibitors of both enzymes partly reduced the enhancement. The inhibitors also partly blocked phorbol ester-induced AP-1 activation, which demonstrates a function of these mitogen-activated protein kinases downstream of PKC. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
SH-SY5Y, Reporter gene, Mitogen-activated protein kinases, Protein kinase C, Activating protein-1, Ethanol
in
Alcohol
volume
24
issue
3
pages
189 - 195
publisher
Elsevier
external identifiers
  • pmid:11557304
  • scopus:0034857234
ISSN
0741-8329
DOI
10.1016/S0741-8329(01)00151-3
language
English
LU publication?
yes
id
e0b87221-94a8-4639-8742-a67813aab0cf (old id 1119920)
date added to LUP
2008-06-27 13:41:28
date last changed
2018-05-29 09:38:31
@article{e0b87221-94a8-4639-8742-a67813aab0cf,
  abstract     = {This study demonstrates a method for studying the effects of ethanol on transcription mediated by activating protein-1 (AP-1). The effects of ethanol on AP-1 activity and on the signaling cascades in this process were investigated by using a reporter gene technique with secreted alkaline phosphatase as the reporter gene coupled to nine DNA AP-1-binding elements. Long-term ethanol exposure (48-72 h) dose dependently enhanced AP-1 transcriptional activity in SH-SY5Y cells. Shorter exposure periods with ethanol did not influence AP-1 transcriptional activity compared with findings for control cells. Inhibition of protein kinase C (PKC) dramatically decreased AP-1 activity in both control and ethanol-exposed cells and abolished the ethanol enhancement. This finding suggests a pivotal role for PKC-coupled signaling in AP-1 transcriptional activity. Phorbol ester stimulation of AP-1 transcriptional activity was not influenced by long-term ethanol exposure. This finding indicates that signaling events upstream of PKC are the targets for ethanol. Mitogen-activated protein kinases ERK and p38 may play a role in ethanol-enhanced AP-1 activity because inhibitors of both enzymes partly reduced the enhancement. The inhibitors also partly blocked phorbol ester-induced AP-1 activation, which demonstrates a function of these mitogen-activated protein kinases downstream of PKC.},
  author       = {Fried, Ulrik and Kotarsky, Knut and Alling, Christer},
  issn         = {0741-8329},
  keyword      = {SH-SY5Y,Reporter gene,Mitogen-activated protein kinases,Protein kinase C,Activating protein-1,Ethanol},
  language     = {eng},
  number       = {3},
  pages        = {189--195},
  publisher    = {Elsevier},
  series       = {Alcohol},
  title        = {Chronic ethanol exposure enhances activating protein-1 transcriptional activity in human neuroblastoma cells},
  url          = {http://dx.doi.org/10.1016/S0741-8329(01)00151-3},
  volume       = {24},
  year         = {2001},
}