Ghosh Sharmistha, Hevi Sarah, Chuck Steven L
Molecular Medicine Unit, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Blood. 2004 Mar 15;103(6):2369-76. doi: 10.1182/blood-2003-09-3050. Epub 2003 Nov 13.
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.
血清铁蛋白在临床医学中已被广泛用作铁储备和炎症的指标。循环铁蛋白也可产生旁分泌作用。尽管血清铁蛋白具有临床意义，但其分泌仍然是个谜。目前的共识观点是血清铁蛋白来源于组织铁蛋白——主要是轻链铁蛋白，其可以被糖基化。铁蛋白重链和轻链是胞质蛋白，它们形成由24个亚基组成的笼状结构以储存细胞内铁。我们发现，当稳定转染的HepG2细胞或腺病毒感染的HepG2细胞中轻链铁蛋白的表达增加时，轻链铁蛋白会被分泌。分泌通过经典分泌途径进行，一些链会进行N-糖基化。铁蛋白在分泌之前不需要形成笼状结构。血清中的一种因子能特异性、有效且快速地阻断分泌。这种对铁蛋白分泌的抑制时机表明，尽管没有传统的信号序列，但正常情况下胞质中的轻链铁蛋白在翻译过程中会被靶向分泌途径。因此，糖基化和未糖基化铁蛋白的分泌是一个受调控的过程，而非随机过程。
