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Effects of ethanol on the expression of immediate-early genes in nerve cells

Ding, Wei-Qun LU (1998)
Abstract
Immediate-early genes of the fos and jun families encode proteins that dimerize to form a complex of activator protein 1 and regulate the expression of a number of genes in the nervous system. Ethanol has previously been shown to induce alterations in expression of fos and jun genes in the brain. The present study examined the effects of ethanol on the expression of c-fos, fosB, c-jun, junB and junD genes in human neuroblastoma SH-SY5Y cells. Prior to the investigation of ethanol effects, the basal and agonist-stimulated expression of these genes were characterized. A constitutive expression of c-jun and junD was observed in unstimulated cells, whereas transcripts of c-fos, fosB and junB could not be detected. Stimulation with carbachol... (More)
Immediate-early genes of the fos and jun families encode proteins that dimerize to form a complex of activator protein 1 and regulate the expression of a number of genes in the nervous system. Ethanol has previously been shown to induce alterations in expression of fos and jun genes in the brain. The present study examined the effects of ethanol on the expression of c-fos, fosB, c-jun, junB and junD genes in human neuroblastoma SH-SY5Y cells. Prior to the investigation of ethanol effects, the basal and agonist-stimulated expression of these genes were characterized. A constitutive expression of c-jun and junD was observed in unstimulated cells, whereas transcripts of c-fos, fosB and junB could not be detected. Stimulation with carbachol and TPA induced expression of all these genes but the expression patterns differed among individual genes. The expression of c-fos, fosB and junB induced by carbachol was primarily mediated through protein kinase C, whereas the carbachol-stimulated expression of c-jun and junD was mainly regulated via calcium/calmodulin-dependent kinase II. Long-term ethanol exposure increased the expression of c-jun and junD and potentiated the carbachol-stimulated expression of c-fos, fosB and junB. On the other hand, acute ethanol selectively attenuated the basal and phorbol ester-stimulated expression of junD, leaving the expression of c-jun and junB unaffected. Thus, junD seems to be sensitive to both acute and long-term ethanol exposure. The potentiation of carbachol-stimulated c-fos, fosB and junB expression after long-term ethanol exposure was primarily mediated via M1 receptors and protein kinase C. Neither long-term nor acute ethanol exposure influenced the degradation of the junD mRNA, which indicates that it is the transcription of the gene which is affected by ethanol. These results support the view that expression of fos and jun genes is involved in the ethanol-induced changes in the function of nerve cells. (Less)
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author
supervisor
opponent
  • Liljequist, Sture, Karolinska Hospital, Stockholm
organization
publishing date
type
Thesis
publication status
published
subject
keywords
neuroadaptation, the central nervous system, AP-1, junD, junB, c-jun, fosB, c-fos, neuroblastoma SH-SY5Y, ethanol, immediate-early genes, Neurology, neuropsychology, neurophysiology, Neurologi, neuropsykologi, neurofysiologi
pages
105 pages
defense location
N/A
defense date
1998-05-06 10:15:00
external identifiers
  • other:ISRN: LUMEDW/MEPS--98/1009--SE
ISBN
91-628-2923-8
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Neurochemistry (ceased) (LUR000012)
id
80a662c1-97f5-423d-afa0-96f36a63a2bb (old id 38517)
date added to LUP
2016-04-04 13:36:04
date last changed
2018-11-21 21:15:03
@phdthesis{80a662c1-97f5-423d-afa0-96f36a63a2bb,
  abstract     = {{Immediate-early genes of the fos and jun families encode proteins that dimerize to form a complex of activator protein 1 and regulate the expression of a number of genes in the nervous system. Ethanol has previously been shown to induce alterations in expression of fos and jun genes in the brain. The present study examined the effects of ethanol on the expression of c-fos, fosB, c-jun, junB and junD genes in human neuroblastoma SH-SY5Y cells. Prior to the investigation of ethanol effects, the basal and agonist-stimulated expression of these genes were characterized. A constitutive expression of c-jun and junD was observed in unstimulated cells, whereas transcripts of c-fos, fosB and junB could not be detected. Stimulation with carbachol and TPA induced expression of all these genes but the expression patterns differed among individual genes. The expression of c-fos, fosB and junB induced by carbachol was primarily mediated through protein kinase C, whereas the carbachol-stimulated expression of c-jun and junD was mainly regulated via calcium/calmodulin-dependent kinase II. Long-term ethanol exposure increased the expression of c-jun and junD and potentiated the carbachol-stimulated expression of c-fos, fosB and junB. On the other hand, acute ethanol selectively attenuated the basal and phorbol ester-stimulated expression of junD, leaving the expression of c-jun and junB unaffected. Thus, junD seems to be sensitive to both acute and long-term ethanol exposure. The potentiation of carbachol-stimulated c-fos, fosB and junB expression after long-term ethanol exposure was primarily mediated via M1 receptors and protein kinase C. Neither long-term nor acute ethanol exposure influenced the degradation of the junD mRNA, which indicates that it is the transcription of the gene which is affected by ethanol. These results support the view that expression of fos and jun genes is involved in the ethanol-induced changes in the function of nerve cells.}},
  author       = {{Ding, Wei-Qun}},
  isbn         = {{91-628-2923-8}},
  keywords     = {{neuroadaptation; the central nervous system; AP-1; junD; junB; c-jun; fosB; c-fos; neuroblastoma SH-SY5Y; ethanol; immediate-early genes; Neurology; neuropsychology; neurophysiology; Neurologi; neuropsykologi; neurofysiologi}},
  language     = {{eng}},
  school       = {{Lund University}},
  title        = {{Effects of ethanol on the expression of immediate-early genes in nerve cells}},
  year         = {{1998}},
}