Zinc modulation of insulin-like growth factor's effect in osteoblastic MC3T3-E1 cells.
Whether the anabolic effect of insulin-like growth factor-I (IGF-I) in osteoblastic MC3T3-E1 cells is modulated by zinc, an activator of bone formation, was investigated in vitro. After subculture for 3 days, the cells were cultured for 72 h with IGF-I (10(-8) M). The peptide produced a significant increase of protein concentration, deoxyribonucleic acid (DNA) content, and cell number in the cells. These increases were markedly enhanced by the presence of zinc sulfate (10(-5) M), but not zinc-chelating dipeptide (beta-alanyl-L-histidinato zinc; 10(-5) M). Also, the cellular alkaline phosphatase activity was synergistically increased by the presence of both IGF-I and zinc sulfate. Thus, effect was not seen in the presence of both insulin (10(-8) M) and zinc sulfate (10(-5) M). The effect of zinc sulfate to enhance the IGF-I-increased alkaline phosphatase activity and protein concentration in the cells was clearly prevented by the presence of cycloheximide (10(-6) M), staurosporin (10(-8) M), or okadaic acid (10(-7) M) with an effective concentration. However, staurosporin had a partial inhibiting effect on the IGF-I or the IGF-I plus zinc-induced increases in cellular protein, although okadaic acid entirely blocked the IGF-I or the IGF-I plus zinc effect. The present study demonstrates that the anabolic effect of IGF-I in osteoblastic cells is enhanced by zinc ion. The enhancement by zinc may be mediated through the signaling pathway of protein kinase C and protein phosphatase in the cells.
Laboratory of Metabolism and Endocrinology, Graduate School of Nutritional Sciences, University of Shizuoka, Japan.
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Matsui
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Yamaguchi
D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002336:Carnosine / Q000031:analogs & derivatives / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D019319:Okadaic Acid; D009942:Organometallic Compounds / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D019311:Staurosporine; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology*; D017967:Zinc Compounds
D000470:Alkaloids; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D007328:Insulin; D009942:Organometallic Compounds; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D017967:Zinc Compounds; C061957:polaprezinc; D019319:Okadaic Acid; D007334:Insulin-Like Growth Factor I; D002336:Carnosine; D004247:DNA; D003513:Cycloheximide; D000469:Alkaline Phosphatase; D019311:Staurosporine; D015032:Zinc