title: Astrocyte growth is regulated by neuropeptides through Tis 8 and basic fibroblast growth factor.
abstract: The important intracellular mechanisms of astrocyte growth are not well defined. Using an inhibitor of astrocyte proliferation, atrial natriuretic peptide (ANP), and the glial mitogen endothelin (ET-3), we sought a common pathway for growth regulation in these neural cells. In cultured fetal rat diencephalic astrocytes, ANP selectively and rapidly inhibited the Tis 8 immediate early gene and protein. After 4 h, ANP selectively inhibited the basic fibroblast growth factor (bFGF) gene and protein. ET-3 significantly stimulated both Tis 8 and bFGF mRNAs and protein, but also stimulated several other immediate early and growth factor/receptor genes. An antisense oligonucleotide to Tis 8 strongly prevented ET-stimulated thymidine incorporation, while the inhibitory action of ANP was enhanced. The Tis 8 antisense oligonucleotide also significantly reversed ET-stimulated bFGF transcription and enhanced the bFGF inhibition caused by ANP. In addition, an antisense oligonucleotide to bFGF significantly reversed the ET-stimulated thymidine incorporation and enhanced the ANP inhibition of DNA synthesis. The sequential modulation of Tis 8, followed by bFGF, provides a novel mechanism for both positive and negative regulation of astrocyte growth by endogenous neuropeptides.
authors.affiliation: Department of Medicine, University of California at Irvine 92717.
authors.forename: R M
authors.initials: RM
authors.lastname: Hu
authors.forename: E R
authors.initials: ER
authors.lastname: Levin
mesh_terms: D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000502:physiology*; D051766:Early Growth Response Protein 1; D016232:Endothelins / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D016232:Endothelins; D017874:Immediate-Early Proteins; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D009320:Atrial Natriuretic Factor; D004247:DNA