Novel lymphocyte growth-inhibiting tripeptide: N-acetyl-glu-ser-GlyNH(2).
The limited and predetermined number of cells that constitutes an organ or specialized cell population is to all appearances regulated according to a negative feedback principle involving growth inhibitors with sufficient tissue specificity. To find growth-inhibiting factors in lymphoid cells, we followed established purification procedures and assays. We found a single-peak fraction in water extracts of dog spleen homogenates that inhibited proliferation of Molt (T cell) lymphoma cells at low concentrations in vitro, with no significant effect on a B cell lymphoma cell line (Ramos). C-terminal amino acid sequencing and MS analysis showed the factor to be a tripeptide: N-acetyl-Glu-Ser-GlyNH(2). Treatment with a synthetic tripeptide with the structure N-acetyl-Glu-Ser-GlyNH(2) decreased the number of cell doublings of Molt cells. The peptide also delayed cell flux at the G(2)-M transition of the cell cycle, while incorporation of tritiated thymidine was not altered at the examined time points in this cell line. However, DNA synthesis in PPD-stimulated normal human lymphocytes was significantly inhibited and with a bell-shaped dose-response curve.
Liu
Y
Y
Pediatric Research Institute, University of Oslo, Oslo, N-0027, Norway.
Elgjo
K
K
Wright
M
M
Reichelt
K L
KL
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004285:Dogs; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology; D020539:Sequence Analysis, Protein; D013154:Spleen / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C416671:N-acetylglutamyl-seryl-glycinamide; D009842:Oligopeptides; D010455:Peptides