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

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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.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Substance Abuse

Keywords

  • SH-SY5Y, Reporter gene, Mitogen-activated protein kinases, Protein kinase C, Activating protein-1, Ethanol
Original languageEnglish
Pages (from-to)189-195
JournalAlcohol
Volume24
Issue number3
Publication statusPublished - 2001
Publication categoryResearch
Peer-reviewedYes