Stimulatory effect of beta-alanyl-L-histidinato zinc on cell proliferation is dependent on protein synthesis in osteoblastic MC3T3-E1 cells

Mol Cell Biochem. 1993 May 12;122(1):59-64. doi: 10.1007/BF00925737.


The effect of beta-alanyl-L-histidinato zinc (AHZ) on bone metabolism was investigated in osteoblastic MC3T3-E1 cells. Cells were cultured for 3 days at 37 degrees C in a CO2 incubator in plastic dishes containing alpha-modified minimum essential medium supplemented with 10% fetal bovine serum. After the cultures, the medium was exchanged for that containing 0.1% bovine serum albumin plus various concentrations of AHZ or other reagents, and the cells were cultured further for appropriate periods of time. The presence of AHZ (10(-7)-10(-5) M) stimulated the proliferation of cells. AHZ (10(-6) and 10(-5) M) increased deoxyribonucleic acid (DNA) content in the cells with 48 hr-culture. This increase was completely blocked by the presence of cycloheximide (10(-6) M) or hydroxyurea (10(-3) M). Also, the presence of cycloheximide (10(-6) M) completely inhibited the AHZ (10(-5) M)-induced increase in the proliferation of cells. Meanwhile, parathyroid hormone (10(-7) M), estrogen (10(-9) M) and insulin (10(-8) M) significantly increased cellular DNA content. However, these hormonal effects clearly lowered in comparison with that of AHZ (10(-5) M). Dibutyryl cyclic AMP (10(-4) M) and zinc sulfate (10(-5) M) did not cause a significant increase in cellular DNA content. The present results support the view that AHZ has a direct specific proliferative effect on osteoblastic cells in vitro and that this effect is dependent on protein synthesis.

MeSH terms

  • Carnosine* / analogs & derivatives*
  • Cell Division / drug effects
  • Cycloheximide / pharmacology
  • DNA / analysis
  • DNA / drug effects
  • Dipeptides / pharmacology*
  • Glucose / metabolism
  • Hydroxyurea / pharmacology
  • Organometallic Compounds / pharmacology*
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Protein Biosynthesis*
  • Zinc / pharmacology*
  • Zinc Compounds


  • Dipeptides
  • Organometallic Compounds
  • Zinc Compounds
  • polaprezinc
  • Carnosine
  • DNA
  • Cycloheximide
  • Glucose
  • Zinc
  • Hydroxyurea