Inhibition of astroglial cell proliferation by alcohols: Interference with the protein kinase C-phospholipase D signaling pathway
Kötter, K; Jin, S; Klein, J
HERO ID
783555
Reference Type
Journal Article
Year
2000
Language
English
PMID
| HERO ID | 783555 |
|---|---|
| In Press | No |
| Year | 2000 |
| Title | Inhibition of astroglial cell proliferation by alcohols: Interference with the protein kinase C-phospholipase D signaling pathway |
| Authors | Kötter, K; Jin, S; Klein, J |
| Journal | International Journal of Developmental Neuroscience |
| Volume | 18 |
| Issue | 8 |
| Page Numbers | 825-831 |
| Abstract | Ethanol inhibits astroglial cell proliferation, an effect that may contribute to the development of alcoholic embryopathy in humans. In the present study, we investigated inhibitory effects of ethanol and butanol isomers (1-, 2- and t-butanol) on astroglial cell proliferation induced by the strongly mitogenic phorbol ester, 4beta-phorbol-12alpha,13beta-dibutyrate (PDB). 4beta-Phorbol-12alpha,13beta-dibutyrate (PDB) induced a 10-fold increase of [3H] thymidine incorporation in cortical astrocytes prepared from newborn rats (EC50: 70 nM) which was blocked by Ro 31-8220, a cell-permeable protein kinase C (PKC) inhibitor. Ethanol blocked PDB-induced astroglial proliferation in a concentration-dependent manner; significant effects were already seen at 0.1% (v/v). Concomitantly, ethanol caused the formation of phosphatidylethanol (PEth) by phospholipase D (PLD) and reduced PLD-mediated formation of phosphatidic acid (PA). The butanols also inhibited the mitogenic action of phorbol ester; the inhibitory potency of the butanols was 1-butanol > 2-butanol > t-butanol. The same range of potencies was observed for the inhibitory activity of the butanols towards protein kinase C activity measured in vitro. At 0.3% concentration, 1-butanol potently suppressed the PDB-induced formation of phosphatidic acid while 2- and t-butanol were less active. Taken together, our results suggest that ethanol and 1-butanol exert a specific inhibitory effect on PKC-dependent astroglial cell proliferation by synergistically inhibiting PKC activity and the PLD signaling pathway. |
| Doi | 10.1016/S0736-5748(00)00044-7 |
| Pmid | 11154852 |
| Wosid | WOS:000165967400012 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000165967400012 |
| Is Public | Yes |
| Language Text | English |
| Keyword | astrocytes; phorbol ester; protein kinase C; phospholipase D; ethanol; butanol; cell proliferation |
| Is Qa | No |