Effect of zinc-chelating dipeptides on osteoblastic MC3T3-E1 cells: activation of aminoacyl-tRNA synthetase

Peptides. 1994;15(8):1367-71. doi: 10.1016/0196-9781(94)90110-4.

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.

MeSH terms

  • 3T3 Cells
  • Alkaline Phosphatase / metabolism
  • Amino Acyl-tRNA Synthetases / metabolism*
  • Animals
  • Carnosine / analogs & derivatives
  • Carnosine / pharmacology
  • Cell Division / drug effects
  • Chelating Agents / pharmacology*
  • Cycloheximide / pharmacology
  • DNA / metabolism
  • Dipeptides / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Histidine / analogs & derivatives
  • Histidine / pharmacology
  • Kinetics
  • Leucine-tRNA Ligase / metabolism
  • Mice
  • Organometallic Compounds / pharmacology
  • Osteoblasts / enzymology*
  • Proteins / metabolism
  • Sulfates / pharmacology*
  • Zinc Compounds / pharmacology*
  • Zinc Sulfate

Substances

  • Chelating Agents
  • Dipeptides
  • Organometallic Compounds
  • Proteins
  • Sulfates
  • Zinc Compounds
  • di(N-acetylalanyl-histidinato)zinc
  • di(histidino)zinc
  • polaprezinc
  • Histidine
  • Zinc Sulfate
  • Carnosine
  • DNA
  • Cycloheximide
  • Alkaline Phosphatase
  • Amino Acyl-tRNA Synthetases
  • Leucine-tRNA Ligase