Journal article
Effects of glia maturation factor overexpression in primary astrocytes on MAP kinase activation, transcription factor activation, and neurotrophin secretion
Neurochemical research, Vol.26(12), pp.1293-1299
2001
DOI: 10.1023/A:1014241300179
PMID: 11885780
Abstract
Using the replication-defective adenovirus vector, we overexpressed rat glia maturation factor (GMF) in primary astrocyte cultures derived from embryonic rat brains. Among the three isoforms of MAP kinase, there was a big increase in the phosphorylation of p38, as detected with Western blotting using the phosphospecific antibody. Likewise, there was a substantial increase in the phosphorylation of the transcription factor CREB. Using the electrophoretic mobility shift assay (EMSA), we found a stimulation in the transcription factor NF-kappaB. The activations of CREB and NF-kappaB were blocked by inhibitors of either p38 (SB-203580) or MEK (PD-098059), suggesting that they were events downstream of MAK kinase. There was an increased secretion of BDNF and NGF into the conditioned medium, along with an increase in their messenger RNA. The inductions of BDNF and NGF were also blocked by inhibitors of p38 and MEK, as well as by the inhibition of NF-kappaB with a decoy DNA sequence. Taken together, the results suggest that GMF functions intracellularly in astrocytes as a modulator of MAP kinase signal transduction, leading to a series of downstream events including CREB and NF-kappaB activation, resulting in the induction and secretion of the neurotrophins.
Details
- Title: Subtitle
- Effects of glia maturation factor overexpression in primary astrocytes on MAP kinase activation, transcription factor activation, and neurotrophin secretion
- Creators
- Asgar ZAHEER - Department of Neurology (Division of Neurochemistry and Neurobiology), Veterans Affairs Medical Center and the University of Iowa College of Medicine, Iowa City, IA 52242, United StatesMark A YOREK - Department of Internal Medicine (Diabetes-Endocrinology Research Center), Veterans Affairs Medical Center and the University of Iowa College of Medicine, Iowa City, IA 52242, United StatesRamon LIM - Department of Internal Medicine (Diabetes-Endocrinology Research Center), Veterans Affairs Medical Center and the University of Iowa College of Medicine, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Neurochemical research, Vol.26(12), pp.1293-1299
- Publisher
- Springer
- DOI
- 10.1023/A:1014241300179
- PMID
- 11885780
- ISSN
- 0364-3190
- eISSN
- 1573-6903
- Language
- English
- Date published
- 2001
- Academic Unit
- Neurology; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094655702771
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