Alam J, Smith A
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70112.
J Biol Chem. 1989 Oct 25;264(30):17637-40.
Hemopexin (HPX) transports heme to liver parenchymal cells, undergoes receptor-mediated endocytosis, and recycles intact. Incubation of mouse hepatoma (Hepa) cells with heme-HPX causes a rapid dose- and time-dependent increase in the steady-state level of heme oxygenase (HO) mRNA. A maximum induction of 20-25-fold is achieved within 3 h after incubation with 10 microM heme-HPX. This accumulation of HO mRNA results primarily from increased transcription of the HO gene as judged by in vitro nuclear run-on assays. In addition, receptor-mediated transport of heme into Hepa cells significantly decreases the steady-state level of transferrin receptor (TfR) mRNA. While a 25-30-fold decrease in the amount of TfR mRNA is observed within 3 h of incubation of Hepa cells with 10 microM heme-HPX, no significant change in the rate of TfR gene transcription was detected. These regulatory effects of heme-HPX are not restricted to hepatic cells but are also observed in human promyelocytic HL-60 cells. This is the first direct demonstration of receptor-mediated transport of heme by hemopexin regulating gene expression in mammalian cells.
血红素结合蛋白（HPX）将血红素转运至肝实质细胞，经受体介导的内吞作用后完整循环利用。用血红素-HPX孵育小鼠肝癌（Hepa）细胞会导致血红素加氧酶（HO）mRNA的稳态水平迅速出现剂量和时间依赖性增加。用10微摩尔血红素-HPX孵育3小时内可实现20至25倍的最大诱导。根据体外细胞核连续转录分析判断，HO mRNA的这种积累主要源于HO基因转录增加。此外，受体介导的血红素转运进入Hepa细胞会显著降低转铁蛋白受体（TfR）mRNA的稳态水平。在用10微摩尔血红素-HPX孵育Hepa细胞3小时内可观察到TfR mRNA量减少25至30倍，但未检测到TfR基因转录速率有显著变化。血红素-HPX的这些调节作用不仅限于肝细胞，在人早幼粒细胞HL-60细胞中也可观察到。这是首次直接证明血红素结合蛋白通过受体介导的血红素转运调节哺乳动物细胞中的基因表达。
