Glucagon-like peptide-2 stimulates the proliferation of cultured rat astrocytes.
Glucagon-like peptide-2 (GLP-2) is a potent intestinotrophic/satiety hormone that acts through a G protein-coupled receptor. To determine whether or not GLP-2 has any effect on cellular proliferation on neural cells, we examined the effects of this peptide on cultured astrocytes from rat cerebral cortex. The expression of the GLP-2 receptor gene in both cerebral cortex and astrocytes was determined by RT-PCR and Southern blotting. Also, cells responded to GLP-2, producing cAMP in a dose-dependent manner (EC50 = 0.86 nm). GLP-2 also stimulated the DNA synthesis rate in rat astrocytes. When proliferation was assessed by measuring [3H]thymidine incorporation into DNA or staining cells with crystal violet, GLP-2 produced a dose-dependent increase in both parameters. Similarly, when the numbers of cells in different phases of the cell cycle were measured by flow cytometry, a dose-dependent decrease in those in the G0-G1 phase and an increase in those in the S and G2-M phases were observed after 24 h incubation with GLP-2. By contrast, the number of hypodiploid cells was not affected during the experimental time. Also, GLP-2 produced a significant increase in the mRNAs of c-fos and c-jun when gene expression was determined by Northern blotting. These results suggest that GLP-2 directly stimulates the proliferation of rat astrocytes; this may open new insights in the physiological role of this novel neuropeptide.
Velázquez
Esther
E
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
Ruiz-Albusac
Juan M
JM
Blázquez
Enrique
E
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015152:Blotting, Northern; D015139:Blotting, Southern; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA / Q000032:analysis / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D010455:Peptides / Q000494:pharmacology* / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D014316:Tritium
D053767:Glucagon-Like Peptide 2; D010455:Peptides; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014316:Tritium; D004763:Glucagon-Like Peptides; D004247:DNA; D000242:Cyclic AMP