Yorek M A, Conner C E, Spanheimer R G
Department of Internal Medicine, Veterans Affairs Medical Center, Iowa City, IA 52246, USA.
J Cell Physiol. 1995 Dec;165(3):658-66. doi: 10.1002/jcp.1041650325.
L-fucose is a monosaccharide which is present in low concentrations in normal serum but is increased in diabetes, cancer, and inflammatory diseases. The contribution that abnormal L-fucose levels make to the progression of these disorders is unknown. In a previous study we showed that increased L-fucose concentration reduced proliferation and proteoglycan production by cultured cerebral microvessel endothelial cells. In the present study we show that exposing cerebral microvessel endothelial cells for 2 weeks to medium containing an increased concentration of L-fucose causes a significant decrease in collagen and to a lesser extent noncollagen protein production. The effect of L-fucose on collagen and noncollagen protein production is concentration-dependent: 1 mM L-fucose causes a significant decrease in collagen production but has no effect on noncollagen protein production; a 5 mM L-fucose concentration causes a maximum decrease in both collagen and noncollagen protein production. This defect is unrelated to the reduction in myo-inositol uptake caused by L-fucose and is not prevented by aminoguanidine. Collagen production can be improved by restoring L-fucose-conditioned cells to normal medium. Culturing cells for 2 weeks in medium containing 10 mM L-fucose resulted in a 50% decrease in collagen production, which was restored to 75% of control after cells were transferred to normal medium for 7 days. In contrast, noncollagen protein production was totally restored after 3 days in normal medium. Increasing levels of L-fucose in serum of rats also resulted in a decrease in collagen production. Collagenase digestible incorporation of L-[2,3,4,5-3H]proline into protein of the articular cartilage from rats fed a diet containing 20% L-fucose for 3 weeks was reduced by about 40% compared to rats fed a normal diet. The decrease in collagen production in L-fucose fed rats was less than the reduction that occurred in streptozotocin-induced diabetic rats. These data suggest that changes in L-fucose concentration itself may be a factor in the regulation of collagen production.
L-岩藻糖是一种单糖，在正常血清中含量较低，但在糖尿病、癌症和炎症性疾病中会升高。L-岩藻糖水平异常对这些疾病进展的影响尚不清楚。在之前的一项研究中，我们发现L-岩藻糖浓度升高会降低培养的脑微血管内皮细胞的增殖和蛋白聚糖生成。在本研究中，我们发现将脑微血管内皮细胞暴露于含有较高浓度L-岩藻糖的培养基中2周，会导致胶原蛋白显著减少，非胶原蛋白生成也有一定程度减少。L-岩藻糖对胶原蛋白和非胶原蛋白生成的影响呈浓度依赖性：1 mM L-岩藻糖会导致胶原蛋白生成显著减少，但对非胶原蛋白生成无影响；5 mM L-岩藻糖浓度会使胶原蛋白和非胶原蛋白生成均最大程度减少。这种缺陷与L-岩藻糖引起的肌醇摄取减少无关，氨基胍也无法预防。将L-岩藻糖处理过的细胞恢复到正常培养基中可改善胶原蛋白生成。在含有10 mM L-岩藻糖的培养基中培养细胞2周，胶原蛋白生成减少50%，将细胞转移到正常培养基中7天后，可恢复到对照的75%。相比之下，非胶原蛋白生成在正常培养基中培养3天后完全恢复。大鼠血清中L-岩藻糖水平升高也会导致胶原蛋白生成减少。与喂食正常饮食的大鼠相比，喂食含20% L-岩藻糖饮食3周的大鼠关节软骨中，L-[2,3,4,5-³H]脯氨酸的胶原酶可消化掺入蛋白减少约40%。喂食L-岩藻糖的大鼠胶原蛋白生成减少程度小于链脲佐菌素诱导的糖尿病大鼠。这些数据表明，L-岩藻糖浓度的变化本身可能是调节胶原蛋白生成的一个因素。
