title: Effect of zinc-chelating dipeptides on osteoblastic MC3T3-E1 cells: activation of aminoacyl-tRNA synthetase.
abstract: The effect of zinc-chelating dipeptides on osteoblastic MC3T3-E1 cells was investigated. As zinc compounds, we used zinc sulfate, AHZ, di(N-acetyl-beta-alanyl-L-histidinato)zinc (AAHZ), and di(histidino)zinc (HZ). Cells were cultured for 72 h in the presence of zinc compounds (10(-8)-10(-5) M). The effect of AHZ (10(-7) and 10(-6) M) to increase protein and deoxyribonucleic acid (DNA) contents in the cells was the greatest in comparison with those of other zinc compounds. Zinc sulfate and HZ at 10(-7) M did not have an effect on the cellular protein content. AHZ (10(-6) M) had a potent effect on cell proliferation, although zinc sulfate (10(-6) M) had no effect. beta-Alanyl-L-histidine (10(-6) and 10(-5) M) did not have an appreciable effect on the cells. Those effects of AHZ (10(-6) M) on osteoblastic cells were completely abolished by the presence of cycloheximide (10(-6) M). AHZ (10(-8)-10(-5) M) directly activated [3H]leucyl-tRNA synthetase in the cell homogenate, whereas the effect of zinc sulfate was seen at 10(-6) and 10(-5) M. The present study suggests that the chemical form of zinc-chelating beta-alanyl-L-histidine (AHZ) can reveal a potent anabolic effect on osteoblastic cells, and that AHZ directly stimulates protein synthesis.
authors.affiliation: Laboratory of Metabolism and Endocrinology, Graduate School of Nutritional Sciences, University of Shizuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: S
authors.initials: S
authors.lastname: Kishi
authors.forename: M
authors.initials: M
authors.lastname: Hashizume
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000378:metabolism; D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism*; D000818:Animals; D002336:Carnosine / Q000031:analogs & derivatives / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006639:Histidine / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D007935:Leucine-tRNA Ligase / Q000378:metabolism; D051379:Mice; D009942:Organometallic Compounds / Q000494:pharmacology; D010006:Osteoblasts / Q000201:enzymology*; D011506:Proteins / Q000378:metabolism; D013431:Sulfates / Q000494:pharmacology*; D017967:Zinc Compounds / Q000494:pharmacology*; D019287:Zinc Sulfate
chemical_list: D002614:Chelating Agents; D004151:Dipeptides; D009942:Organometallic Compounds; D011506:Proteins; D013431:Sulfates; D017967:Zinc Compounds; C089030:di(N-acetylalanyl-histidinato)zinc; C089031:di(histidino)zinc; C061957:polaprezinc; D006639:Histidine; D019287:Zinc Sulfate; D002336:Carnosine; D004247:DNA; D003513:Cycloheximide; D000469:Alkaline Phosphatase; D000604:Amino Acyl-tRNA Synthetases; D007935:Leucine-tRNA Ligase