Thapsigargin suppresses alpha 1-acid glycoprotein secretion independently of N-glycosylation and ER stress
Thapsigargin suppresses alpha 1-acid glycoprotein secretion independently of N-glycosylation and ER stress
复制标题
Thapsigargin 抑制 α1-酸性糖蛋白分泌，与 N-糖基化和 ER 应激无关
DOI：
10.1016/j.bbrc.2021.03.017
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Iwata H.
中科院分区：
文献类型：
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作者：
Goto N;Shibutani S;Miura N;Watanabe R;Iwata H.
α-1酸性糖蛋白（AGP）是一种主要的急性期蛋白，参与药物/配体结合和免疫应答的调节。响应于炎症，来自肝脏的AGP分泌增加，导致血浆AGP浓度升高。AGP表现出多个N-糖基化位点，因此是高度糖基化的。虽然AGP糖基化被认为影响其功能，但AGP糖基化对其分泌的意义尚不清楚。在这项研究中，我们研究了AGP糖基化的影响，使用糖基化缺陷的小鼠AGP突变体缺乏一个，四个，或所有五个N-糖基化位点。此外，我们研究了内质网（ER）应激诱导试剂，包括衣霉素和毒胡萝卜素，诱导ER应激的N-糖基化依赖性和非依赖性的方式，分别的影响。在这里，我们发现糖基化缺陷和ER应激对AGP分泌的影响很小或没有影响。相反，毒胡萝卜素显着抑制AGP分泌的糖基化非依赖性的方式。这些结果表明，AGP分泌的调节，通过毒胡萝卜素敏感的途径，可能进一步控制细胞内钙浓度。
Alpha-1 acid glycoprotein (AGP) is a major acute-phase protein that is involved in drug/ligand binding and regulation of immune response. In response to inflammation, AGP secretion from the liver increases, resulting in elevated concentration of plasma AGP. AGP exhibits multiple N-glycosylation sites, and thus, is highly glycosylated. Although AGP glycosylation is considered to affect its functions, the significance of AGP glycosylation for its secretion is unclear. In this study, we investigated the effects of AGP glycosylation using glycosylation-deficient mouse AGP mutants lacking one, four, or all five N-glycosylation sites. Furthermore, we examined the effects of endoplasmic reticulum (ER) stress-inducing reagents, including tunicamycin and thapsigargin, which induce ER stress in an N-glycosylation-dependent and -independent manner, respectively. Here, we found that glycosylation deficiency and ER stress induce a little or no effect on AGP secretion. Conversely, thapsigargin significantly suppressed AGP secretion in glycosylation-independent manner. These findings indicate that AGP secretion is regulated via thapsigargin-sensitive pathway that might be further controlled by the intracellular calcium concentrations.