Forstner J, Roomi N, Khorasani R, Kuhns W, Forstner G
Research Institute, Hospital for Sick Children, Toronto, Canada.
Exp Mol Pathol. 1991 Apr;54(2):129-43. doi: 10.1016/0014-4800(91)90026-t.
Biochemical and histochemical parameters of intestinal mucins were examined in control and reserpine-treated rats. An assay for intestinal mucin sulfotransferase was developed and the activity shown to increase 3.4 times over control levels in rats given intraperitonal reserpine (0.5 mg/kg body wt) daily for 7 days. Histochemical staining of intestinal sections revealed an increase in sulfomucins in goblet cells of reserpine-treated rats. The effects were prominent as early as 1 day following injection, particularly in the distal third of the small intestine, and during the next 6 days these changes spread progressively to the middle and proximal thirds. After 3 days of treatment mucins were purified from each intestinal segment and compared to control mucins with respect to composition and [35S]NaSO4 incorporation. Although individual amino acid and carbohydrate molar ratios were unchanged, the total carbohydrate and sulfate content of mucins in treated animals was elevated (two to three times above control) in the middle and distal thirds of the intestine. In vivo [35S]SO4 incorporation into these mucins was also proportionaltely elevated, and was targetted to O-linked oligosaccharide side chains. These findings are consistent with an action of reserpine causing an increased production of mucin which is enriched in glycoprotein components bearing sulfated oligosaccharide chains. The relevance of these findings to the production of hypersulfated and hyperglycosylated mucins in cystic fibrosis is discussed.
在对照大鼠和利血平处理的大鼠中检测了肠道粘蛋白的生化和组织化学参数。开发了一种肠道粘蛋白磺基转移酶测定方法，结果显示，每天腹腔注射利血平（0.5mg/kg体重），持续7天的大鼠，其活性比对照水平增加了3.4倍。肠道切片的组织化学染色显示，利血平处理的大鼠杯状细胞中的硫粘蛋白增加。这些影响在注射后1天就很明显，尤其是在小肠远端三分之一处，在接下来的6天里，这些变化逐渐蔓延到中间和近端三分之一处。治疗3天后，从每个肠段纯化粘蛋白，并与对照粘蛋白在组成和[35S]NaSO4掺入方面进行比较。虽然单个氨基酸和碳水化合物的摩尔比没有变化，但处理动物肠道中间和远端三分之一处粘蛋白的总碳水化合物和硫酸盐含量升高（比对照高两到三倍）。体内[35S]SO4掺入这些粘蛋白的量也相应增加，并且靶向O-连接寡糖侧链。这些发现与利血平的作用一致，即导致粘蛋白产量增加，而粘蛋白富含带有硫酸化寡糖链的糖蛋白成分。讨论了这些发现与囊性纤维化中高硫酸化和高糖基化粘蛋白产生的相关性。
