RESUMO
NUCB2¹â»8³ has been recently reported as an anorexigenic and anti-hyperglycemic peptide. Here we report that NUCB2¹â»8³ promotes osteogenesis. It was found after two months of once-a-day intravenous injection of NUCB2¹â»8³, bone mineral density of femora and lumbar vertebrae were increased in ovariectomized rats. NUCB2¹â»8³ also increased the alkaline phosphatase activity and promoted mineralization in mouse MC3T3-E1 preosteoblastic cell line. When either both Arg6° and Arg6³ or Ser7² were mutated to Ala, the pro-osteogenic activity was completely lost, indicating that these residues are structurally important for its biological function. Furthermore, it encumbered osteoclastic differentiation of RAW 264.7 macrophage. It also excluded any possibility of the effect caused by contaminants or experimental faults, and demonstrated that the pro-osteogenic activity observed was a specific effect of NUCB2¹â»8³ itself. These findings warranted that further studies on NUCB2¹â»8³ would be valuable for the treatment of bone metabolic diseases especially for osteoporosis.
Assuntos
Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/farmacologia , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/farmacologia , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/farmacologia , Osteogênese/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Densidade Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular , Proteínas de Ligação a DNA/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Proteínas do Tecido Nervoso/genética , Nucleobindinas , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Ovariectomia , Ligante RANK/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
In this paper, a solution culture experiment was conducted to study the effects of environmental factors on Cd biotoxicity and phytochelatins (PCs) production in wheat. The results showed that Cd stress had significant inhibitory effects on wheat growth and PCs overproduction. The Cd biotoxicity and Cd uptake by wheat were affected in varying degrees by soil pH, Ca and S, and the levels of PCs production in root were consistent with the changes of Cd biotoxicity. Furthermore, the Cd biotoxicity was decreased with increasing P supply, coinciding with the decrease of PCs level in root. Mg had no obvious effect on both Cd biotoxicity and PCs level in root. The present results further confirmed that the induced PCs production level by Cd was related to Cd biotoxicity in plant, suggesting that PCs could be a promising biomarker for estimating Cd phytotoxicity.