Stimulatory effect of beta-alanyl-L-histidinato zinc on bone formation in tissue culture.
The present investigation was undertaken to clarify the in vitro effect of beta-alanyl-L-histidinato zinc (AHZ) on bone metabolism in tissue culture. Calvaria were removed from weanling rats (3-week-old male) and cultured for periods up to 96 h in Dulbecco's modified Eagle medium (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin. The experimental cultures contained 10(-8) to 10(-4) mol/l AHZ. The bone cellular zinc content was significantly increased in cultures with concentrations of AHZ greater than 10(-6) mol/l. With 10(-5) mol/l zinc sulfate, the bone cellular zinc content was significantly elevated. Bone calcium content was significantly increased by the presence of 10(-7) to 10(-4) mol/l AHZ. This increase was blocked by the presence of 10(-7) mol/l cycloheximide. Bone alkaline phosphatase activity was elevated in the presence of AHZ (10(-7) to 10(-4) mol/l), whereas it did not significantly alter acid phosphatase activity Bone collagen and DNA contents were significantly increased by 10(-7) to 10(-5) mol/l AHZ, while they were not significantly elevated by zinc sulfate (10(-7) and 10(-6) mol/l). The AHZ (10(-5) mol/l)-induced increase in bone alkaline phosphatase activity and DNA content were prevented by 10(-4) mol/l dipicolinate, a chelator of zinc. Furthermore, the AHZ (10(-5) mol/l)-induced increase in bone alkaline phosphatase activity, collagen and DNA contents were blocked by 10(-7) mol/l cycloheximide. These findings indicate that AHZ had a direct stimulatory effect on bone mineralization in vitro, and that bone protein synthesis was a necessary component of this response. The AHZ effect was more intensive than that of zinc sulfate.
Yamaguchi
M
M
Department of Environmental Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Miwa
H
H
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001846:Bone Development / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002336:Carnosine / Q000031:analogs & derivatives*; D046508:Culture Techniques; D004247:DNA / Q000378:metabolism; D004151:Dipeptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology; D017967:Zinc Compounds; D019287:Zinc Sulfate
D000897:Anti-Ulcer Agents; D004151:Dipeptides; D009942:Organometallic Compounds; D013431:Sulfates; D017967:Zinc Compounds; C061957:polaprezinc; D019287:Zinc Sulfate; D002336:Carnosine; D004247:DNA; D000469:Alkaline Phosphatase; D015032:Zinc; D002118:Calcium