EFFECT OF ZINC-CHELATING DIPEPTIDES ON OSTEOBLASTIC MC3T3-E1 CELLS - ACTIVATION OF AMINOACYL-TRANSFER-RNA 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-beta-alanyl-L-histidinato)zinc (AAHZ), and di(histidino)zinc (H Z). 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 pr otein and deoxyribonucleic acid (DNA) contents in the cells was the gr eatest 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 cont ent. AHZ (10(-6) M) had a potent effect on cell proliferation, althoug h 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. Thos e effects of AHZ (10(-6) M) on osteoblastic cells were completely abol ished by the presence of cycloheximide (10(-6) M). AHZ (10(-8)-10(-5) M) directly activted [H-3]leucyl-tRNA synthetase in the cell homogenat e, 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 b eta-alanyl-L-histidine (AHZ) can reveal a potent anabolic effect on os teoblastic cells, and that AHZ directly stimulates protein synthesis.