Ryan L M, Kurup I, Cheung H S
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Matrix. 1991 Aug;11(4):276-81. doi: 10.1016/s0934-8832(11)80235-0.
Ascorbate (0-500 microM) stimulates synthesis and secretion of collagen by cartilage explants in a dose-dependent fashion as estimated by [3H]proline incorporation. Concurrent elaboration of inorganic pyrophosphate (PPi) parallels [3H]proline incorporation (less than 0.001, Wilcoxon rank sum). The effect on proline and PPi is abolished by ascorbate oxidase. Another reducing agent, Vitamin E, did not promote PPi accumulation about cartilage. Inhibitors of collagen synthesis, including monensin, tumor necrosis factor alpha, and 2',2'dipyridyl also inhibited PPi elaboration. Cycloheximide (1 micrograms/ml) inhibited the ascorbate stimulated PPi elaboration 54% but did not attenuate the secretion of PPi by unstimulated cartilage. Cosecretion of collagen and PPi by chondrocytes may explain these results. Moreover, at least two pathways exist for PPi elaboration, a cycloheximide sensitive path and another independent of new protein synthesis.
抗坏血酸盐(0 - 500微摩尔)以剂量依赖的方式刺激软骨外植体合成和分泌胶原蛋白,这通过[³H]脯氨酸掺入来估算。同时,无机焦磷酸(PPi)的产生与[³H]脯氨酸掺入平行(Wilcoxon秩和检验,P<0.001)。抗坏血酸氧化酶可消除对抗坏血酸盐对脯氨酸和PPi的影响。另一种还原剂维生素E,不会促进软骨周围PPi的积累。胶原蛋白合成抑制剂,包括莫能菌素、肿瘤坏死因子α和2',2'-联吡啶,也会抑制PPi的产生。放线菌酮(1微克/毫升)抑制抗坏血酸盐刺激的PPi产生54%,但不会减弱未受刺激软骨中PPi的分泌。软骨细胞共分泌胶原蛋白和PPi可以解释这些结果。此外,至少存在两条产生PPi的途径,一条对放线菌酮敏感,另一条独立于新的蛋白质合成。