...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular genetics and metabolism >Exogenous mannose does not raise steady state mannose-6-phosphate pools of normal or N-glycosylation-deficient human fibroblasts.
【24h】

Exogenous mannose does not raise steady state mannose-6-phosphate pools of normal or N-glycosylation-deficient human fibroblasts.

机译：外源性甘露糖不会增加正常或N-糖基化缺陷的人类成纤维细胞的稳态甘露糖6-磷酸库。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Increasing intracellular mannose-6-phosphate (Man-6-P) was previously reported to reduce the amount of the major lipid linked oligosaccharide (LLO) precursor of N-glycans; a loss that might decrease cellular N-glycosylation. If so, providing dietary mannose supplements to glycosylation-deficient patients might further impair their glycosylation. To address this question, we studied the effects of exogenous mannose on intracellular levels of Man-6-P, LLO, and N-glycosylation in human and mouse fibroblasts. Mannose (500microM) did not increase Man-6-P pools in human fibroblasts from controls or from patients with Congenital Disorders of Glycosylation (CDG), who have 90-95% deficiencies in either phosphomannomutase (CDG-Ia) or phosphomannose isomerase (MPI) (CDG-Ib), enzymes that both use Man-6-P as a substrate. In the extreme case of fibroblasts derived from Mpi null mice (<0.001% MPI activity), intracellular Man-6-P levels greatly increased in response to exogenous mannose, and this produced a dose-dependent decrease in the steady state level of the major LLO precursor. However, LLO loss did not decrease total protein N-glycosylation or that of a hypoglycosylation indicator protein, DNaseI. These results make it very unlikely that exogenous mannose could impair N-glycosylation in glycosylation-deficient CDG patients.
机译：以前有报道说增加细胞内的6-磷酸甘露糖（Man-6-P）可以减少N-聚糖的主要脂质连接寡糖（LLO）前体的数量;可能会降低细胞N-糖基化的损失。如果是这样，向缺乏糖基化的患者提供膳食甘露糖补充剂可能会进一步损害他们的糖基化。为了解决这个问题，我们研究了外源甘露糖对人和小鼠成纤维细胞中Man-6-P，LLO和N-糖基化的细胞内水平的影响。甘露糖（500microM）不会增加来自对照组或先天性糖基化疾病（CDG）的人成纤维细胞中的Man-6-P库，后者在磷酸甘露糖变酶（CDG-Ia）或磷酸甘露糖异构酶（MPI）中有90-95％的缺陷）（CDG-Ib），都以Man-6-P为底物的酶。在源自Mpi无效小鼠的成纤维细胞的极端情况下（<0.001％MPI活性），细胞内Man-6-P的水平响应于外源性甘露糖而大大增加，并且这导致了主要剂量的稳态水平的剂量依赖性降低LLO前体。但是，LLO的丢失并不会降低总蛋白N-糖基化或降糖基化指示蛋白DNaseI的蛋白质。这些结果使得外源性甘露糖不太可能损害糖基化缺陷型CDG患者的N-糖基化。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号