Lubec G, Labudova O, Seebach D, Beck A, Hoeger H, Hermon M, Weninger M
University of Vienna, Dpt of Paediatrics, Austria.
Life Sci. 1995;57(24):2245-52. doi: 10.1016/0024-3205(95)02217-7.
Collagen type I is the major protein of bone matrix and significantly reduced in osteoporosis. We tested the effect of alpha - methyl - proline on collagen synthesis in the model of the ovariectomized rat. Collagen synthesis was studied at the transcriptional level using Northern and dot blotting and at the protein level using hydroxyproline determination and a specific dye binding collagen assay. Alpha - methyl- proline treatment significantly increased collagen synthesis as compared to untreated ovariectomized and estradiol treated ovariectomized rats and restored collagen synthesis to levels of sham operated rats. Proline analogues were described to stimulate procollagen synthesis at the transcriptional level, however, if incorporated, lead to negative collagen production due to rapid intracellular degradation of the deficient collagen. Our synthesized analogue is not being incorporated, thus not interfering with collagen conformation and can therefore induce collagen production.
I型胶原是骨基质的主要蛋白质,在骨质疏松症中显著减少。我们在去卵巢大鼠模型中测试了α-甲基脯氨酸对胶原合成的影响。使用Northern印迹法和斑点印迹法在转录水平研究胶原合成,使用羟脯氨酸测定法和特异性染料结合胶原测定法在蛋白质水平研究胶原合成。与未处理的去卵巢大鼠和经雌二醇处理的去卵巢大鼠相比,α-甲基脯氨酸处理显著增加了胶原合成,并将胶原合成恢复到假手术大鼠的水平。脯氨酸类似物被描述为在转录水平刺激前胶原合成,然而,如果被掺入,由于缺陷胶原的快速细胞内降解会导致负性胶原产生。我们合成的类似物未被掺入,因此不会干扰胶原构象,因此可以诱导胶原产生。