Regulated secretion of glycosylated human ferritin from hepatocytes
Regulated secretion of glycosylated human ferritin from hepatocytes
复制标题
DOI：
10.1182/blood-2003-09-3050
复制
发表时间：
2004-03-15
期刊：
影响因子：
20.3
通讯作者：
Chuck, SL
中科院分区：
文献类型：
--
作者：
Ghosh, S;Hevi, S;Chuck, SL
血清铁蛋白已广泛应用于临床医学，主要作为铁储备和炎症的指标。循环铁蛋白也有旁分泌作用。尽管血清铁蛋白的临床意义，其分泌仍然是一个谜。一致的观点是血清铁蛋白来源于组织铁蛋白，主要是轻铁蛋白，它可以被糖基化。铁蛋白重链和轻链是细胞质蛋白，形成24个亚基的笼子来储存细胞内的铁。我们发现，当铁蛋白光在稳定转染的HepG2细胞或腺病毒感染的HepG2细胞中表达增加时，会分泌铁蛋白光。输出通过经典的分泌途径发生，一些链被n -糖基化。铁蛋白在分泌前不需要形成笼状。分泌被血清中的一种因子特异性地、有效地、迅速地阻断。铁蛋白分泌抑制的时间表明，尽管缺乏常规的信号序列，正常情况下，胞质铁蛋白L在翻译过程中靶向分泌途径。因此，糖基化和非糖基化铁蛋白的分泌是一个受调节的过程，而不是一个随机过程。(C) 2004年由美国血液病学会出版。
Serum ferritin has been used widely in clinical medicine chiefly as an indicator of iron stores and inflammation. Circulating ferritin also can have paracrine effects. Despite the clinical significance of serum ferritin, its secretion remains an enigma. The consensus view is that serum ferritin arises from tissue ferritins-principally ferritin light-which can be glycosylated. Ferritin heavy and light chains are cytosolic proteins that form cages of 24 subunits to store intracellular iron. We show that ferritin light is secreted when its expression is increased in stable, transfected HepG2 cells or adenovirus-infected HepG2 cells. Export occurs through the classical secretory pathway and some chains are N-glycosylated. Ferritins do not need to form cages prior to secretion. Secretion is blocked specifically, effectively, and rapidly by a factor in serum. The timing of this inhibition of ferritin secretion suggests that normally cytosolic ferritin L is targeted to the secretory pathway during translation despite the absence of a conventional signal sequence. Thus, secretion of glycosylated and unglycosylated ferritin is a regulated and not a stochastic process. (C) 2004 by The American Society of Hematology.