Hickery M S, Bayliss M T
Kennedy Institute of Rheumatology, 6 Bute Gardens, Hammersmith, London W6 7DW, UK.
Biochim Biophys Acta. 1998 Oct 23;1425(2):282-90. doi: 10.1016/s0304-4165(98)00080-4.
Incubation of human articular cartilage explants with interleukin-1alpha (IL-1alpha) inhibited the rate of [35S]sulphate incorporation into glycosaminoglycan (GAG) chains concomitant with an increase in nitric oxide (NO) production. Measurement of the [35S]sulphate showed that IL-1alpha inhibited the synthesis of both keratan sulphate and chondroitin sulphate (CS) chains to a similar extent. This effect was reversed by the NO synthase inhibitor Nomega-iminoethyl-l-ornithine (l-NIO). Analysis of alkali borohydride cleaved GAG chains showed that IL-1alpha had no effect on their size. Similarly when GAG chains were coupled to xyloside the size of the GAG chains attached to the exogenous acceptor decreased but IL-1alpha had no further effect on hydrodynamic size. IL-1alpha did, however, inhibit [35S]sulphate incorporation into xyloside-linked CS chains. In both experiments l-NIO reversed the inhibitory effect on sulphation. Disaccharide analysis of the [35S]GAG chains showed that IL-1alpha preferentially inhibited sulphation of the 6-sulphated isomer and that l-NIO reversed this effect. Thus, IL-1alpha-induced NO mediates the inhibition of sulphate incorporation and alters the sulphation pattern of newly synthesised GAG chains.
用人白细胞介素-1α（IL-1α）孵育人关节软骨外植体，抑制了[35S]硫酸盐掺入糖胺聚糖（GAG）链的速率，同时一氧化氮（NO）生成增加。[35S]硫酸盐的测量结果表明，IL-1α对硫酸角质素和硫酸软骨素（CS）链合成的抑制程度相似。一氧化氮合酶抑制剂Nω-亚氨基乙基-L-鸟氨酸（L-NIO）可逆转这种效应。对碱硼氢化物裂解的GAG链的分析表明，IL-1α对其大小没有影响。同样，当GAG链与木糖苷偶联时，连接到外源性受体上的GAG链大小减小，但IL-1α对流体力学大小没有进一步影响。然而，IL-1α确实抑制了[35S]硫酸盐掺入木糖苷连接的CS链。在这两个实验中，L-NIO都逆转了对硫酸化的抑制作用。对[35S]GAG链的二糖分析表明，IL-1α优先抑制6-硫酸化异构体的硫酸化，而L-NIO可逆转这种效应。因此，IL-1α诱导的NO介导了硫酸盐掺入的抑制作用，并改变了新合成的GAG链的硫酸化模式。
