Truncation of IGF-I yields two mitogens for retinal Müller glial cells.
In the CNS only a truncated form of insulin-like growth factor-I (IGF-I) is detected. Although truncated IGF-I (t-IGF-I) retains mitogenicity, growth promoting activities have not been detected for the tripeptide that is cleaved from IGF-I during truncation. Here, we asked whether the tripeptide is itself a growth factor. Using cultured Müller glial cells from the adult human retina, we found that the cleaved tripeptide, glycine-proline-glutamate, stimulated the proliferation of these cells. Pharmacological experiments indicated that this proliferative effect involves activation of N-methyl-D-aspartate (NMDA) receptors. In addition, t-IGF-I was also mitogenic in our culture system and had an EC50 markedly less than that for IGF-I. Thus, truncation of IGF-I may be a mechanism to augment the mitogenic effect of this gene product by creating a more potent variant and a cleaved tripeptide that is itself a mitogen.
Ikeda
T
T
Department of Ophthalmology, University of Michigan, Ann Arbor 48105, USA.
Waldbillig
R J
RJ
Puro
D G
DG
D000328:Adult; D000595:Amino Acid Sequence; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008934:Mitogens / Q000378:metabolism*; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010786:Photoreceptor Cells / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012160:Retina / Q000166:cytology / Q000378:metabolism*
D008934:Mitogens; D009842:Oligopeptides; D016194:Receptors, N-Methyl-D-Aspartate; D007334:Insulin-Like Growth Factor I; D001973:Bromodeoxyuridine