Islet-neogenesis-associated protein enhances neurite outgrowth from DRG neurons.
Islet-neogenesis-associated protein, INGAP, is a 175-amino-acid pancreatic acinar protein that stimulates pancreatic duct cell proliferation in vitro and islet neogenesis in vivo. To date, the mitogenic activity of INGAP has been identified only in nonneural tissues. The aim of this study was to examine the effects of a pentadecapeptide of INGAP (INGAP peptide), the biologically active portion of the native protein, in cultured dorsal root ganglia (DRG) explants from C57BL/6 mice. The present study provides evidence that INGAP peptide acts as a mitogen in the peripheral nervous system (PNS), and that it enhances neurite outgrowth from DRGs in vitro in a time- and dose-dependent manner. The neuritogenic action of INGAP peptide correlates with an increase in [(3)H]thymidine incorporation (P < 0.0001) and mitochondrial activity (P < 0.001). Results from these studies suggest that INGAP peptide promotes Schwann cell proliferation in the DRG which releases trophic factors that promote neurite outgrowth.
Tam
Joseph
J
Department of Pharmacology and Therapeutics, Department of Surgery, McGill University, 3655 Promenade Sir-William-Osler, Montreal, Quebec, H3G 1Y6, Canada.
Rosenberg
Lawrence
L
Maysinger
Dusica
D
D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002455:Cell Division / Q000187:drug effects; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005562:Formazans / Q000032:analysis; D005727:Ganglia, Spinal / Q000187:drug effects / Q000254:growth & development* / Q000648:ultrastructure; D007700:Kinetics; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure*; D009474:Neurons / Q000648:ultrastructure; D009842:Oligopeptides / Q000494:pharmacology; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000032:analysis; D013936:Thymidine / Q000378:metabolism
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D005562:Formazans; D037181:Lectins, C-Type; D009842:Oligopeptides; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C000612141:REG3A protein, human; C490253:Reg3b protein, mouse; D013778:Tetrazolium Salts; C079782:MTT formazan; D020932:Nerve Growth Factor; D013936:Thymidine