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| OKADAIC ACID INCREASES NERVE GROWTH-FACTOR SECRETION, MESSENGER-RNA STABILITY, AND GENE-TRANSCRIPTION IN PRIMARY CULTURES OF CORTICAL ASTROCYTES |
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| Author(s): PSHENICHKIN SP, WISE BC |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 270 Issue: 11 Pages: 5994-5999 Published: MAR 17 1995 |
| Times Cited: 36 References: 33 |
| Abstract: Neonatal rat cortical astrocytes ire primary culture synthesize and secrete nerve growth factor (NGF) in response to cytokines, growth factors, and activators of protein kinases. To further implicate a protein phosphorylation mechanism in the regulation of NGF expression, astrocytes were treated with okadaic acid and calyculin A, inhibitors of phosphoprotein phosphatases 1 and 2A. Okadaic acid dramatically increased both NGF mRNA content (50-fold) and NGF secretion (100-fold) in astrocytes, while calyculin A, which has a spectrum of phosphatase inhibitory activity different from okadaic acid, failed to augment NGF expression. The increased mRNA accumulation was due mainly to an increase (4-fold) in the half-life of the NGF mRNA following 9 or 24 h of treatment. Nuclear run on assays indicated that okadaic acid also activated NGF gene transcription, which was preceded by an induction of c-fos and c-jun gene transcription. The induction of NGF expression by okadaic acid appeared independent from protein kinase C activity because down-regulating protein kinase C activity failed to decrease the okadaic acid stimulation. In contrast, interleukin-1 beta acted synergistically with okadaic acid to stimulate NGF secretion. The results indicate that okadaic acid profoundly stimulates NGF expression in astrocytes mainly by enhancing NGF mRNA stability and suggest important roles for phosphoprotein phosphatases in regulating NGF production. |
| Document Type: Article |
| Language: English |
Addresses:
1. GEORGETOWN UNIV, MED CTR, DEPT PHARMACOL, WASHINGTON, DC 20007 USA
2. GEORGETOWN UNIV, MED CTR, FIDIA GEORGETOWN INST NEUROSCI, WASHINGTON, DC 20007 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: QM945 |
| ISSN: 0021-9258 |
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