Stimulatory effect of beta-alanyl-L-histidinato zinc on cell proliferation is dependent on protein synthesis in osteoblastic MC3T3-E1 cells.
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.
Hashizume
M
M
Laboratory of Metabolism and Endocrinology, Graduate School of Nutritional Sciences, University of Shizuoka, Japan.
Yamaguchi
M
M
D002336:Carnosine / Q000031:analogs & derivatives*; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000032:analysis / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006918:Hydroxyurea / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D014176:Protein Biosynthesis; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds
D004151:Dipeptides; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D002336:Carnosine; D004247:DNA; D003513:Cycloheximide; D005947:Glucose; D015032:Zinc; D006918:Hydroxyurea