期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 275, 期 3, 页码 1987-1992出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.275.3.1987
关键词
-
资金
- NHLBI NIH HHS [HL37884] Funding Source: Medline
- NICHD NIH HHS [T32 HD07409] Funding Source: Medline
- NIDDK NIH HHS [DK52526] Funding Source: Medline
It is now well known that the addition and trimming of oligosaccharide side chains during post-translational modification play an important role in determining the fate of secretory, membrane, and lysosomal glycoproteins, Recent studies have suggested that trimming of oligosaccharide side chains also plays a role in the degradation of misfolded glycoproteins as a part of the quality control mechanism of the endoplasmic reticulum (ER), In this study, we examined the effect of several inhibitors of carbohydrate processing on the fate of the misfolded secretory protein alpha 1 antitrypsin Z. Retention of this misfolded glycoprotein in the ER of liver cells in the classical form of alpha 1 antitrypsin (alpha 1-AT) deficiency is associated with severe liver injury and hepatocellular carcinoma and lack of its secretion is associated with destructive lung disease/emphysema. The results show marked alterations in the fate of alpha 1 antitrypsin Z (alpha 1-ATZ), Indeed, one glucosidase inhibitor, castanospermine (CST), and two mannosidase inhibitors, kifunensine (RIF) and deoxymannojirimycin (DMJ), mediate marked increases in secretion of alpha 1-ATZ by distinct mechanisms. The effects of these inhibitors on secretion have interesting implications for our understanding of the quality control apparatus of the ER, These inhibitors may also constitute models for development of additional drugs for chemoprophylaxis of liver injury and emphysema in patients with alpha 1-AT deficiency.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据