Laboratory of Veterinary Hygiene, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, 753-8515, Japan.
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, 36849, USA.
Biochem Biophys Res Commun. 2021 May 7;552:30-36. doi: 10.1016/j.bbrc.2021.03.017. Epub 2021 Mar 16.
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.
α-1 酸性糖蛋白（AGP）是一种主要的急性期蛋白，参与药物/配体结合和免疫反应的调节。在炎症反应中，AGP 从肝脏中的分泌增加，导致血浆 AGP 浓度升高。AGP 具有多个 N-糖基化位点，因此高度糖基化。尽管 AGP 糖基化被认为会影响其功能，但 AGP 糖基化对其分泌的意义尚不清楚。在这项研究中，我们使用缺乏一个、四个或全部五个 N-糖基化位点的缺乏糖基化的小鼠 AGP 突变体研究了 AGP 糖基化的影响。此外，我们还研究了内质网（ER）应激诱导剂，包括衣霉素和 thapsigargin 的影响，它们分别以 N-糖基化依赖和非依赖的方式诱导 ER 应激。在这里，我们发现糖基化缺陷和 ER 应激对 AGP 分泌几乎没有影响或没有影响。相反，thapsigargin 以非糖基化依赖的方式显著抑制 AGP 分泌。这些发现表明，AGP 分泌受 thapsigargin 敏感途径调控，该途径可能进一步受细胞内钙离子浓度控制。
