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

The effect of zinc-chelating dipeptides on osteoblastic MC3T3-E1 cells was investigated. As zinc compounds, we used zinc sulfate, AHZ, di(N- acetyl-β- 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. β-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 β-alanyl- l-histidine (AHZ) can reveal a potent anabolic effect on osteoblastic cells, and that AHZ directly stimulates protein synthesis.