Links between cell-surface events involving redox-active copper and gene regulation in the hemopexin heme transport system.
Links between cell-surface events involving redox-active copper and gene regulation in the hemopexin heme transport system.
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涉及氧化还原活性铜的细胞表面事件与血红素血红素运输系统中的基因调控之间的联系。
DOI：
10.1089/ars.2000.2.2-157
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发表时间：
2000
影响因子：
6.6
通讯作者：
Smith,A
中科院分区：
文献类型：
--
作者：
Smith,A
血红素被认为在溶血、创伤和缺血后再灌注的病理学中发挥重要作用。然而，数据稀疏，需要实验模型。通过血红素结合蛋白将血红素转运至组织是一种特定的膜受体介导的过程。血红素结合蛋白像转铁蛋白一样在内吞作用后回收。血红素加氧酶-1 (HO-1)、转铁蛋白、转铁蛋白受体和铁蛋白受血红素-血红素结合蛋白调节。编码对于细胞防御氧化应激很重要的蛋白质的基因，例如富含半胱氨酸的金属硫蛋白 (MT)，也可以被血红素结合蛋白激活，调节细胞周期控制的蛋白质，包括 p21WAF1 和肿瘤抑制因子 p53。正在研究血红素结合蛋白系统，以确定由于血红素结合蛋白受体占据和血红素转运，来自质膜的信号如何影响细胞内事件。蛋白质发生短暂的氧化修饰，表现为羰基的产生。细胞表面的氧化还原过程会产生亚铜离子，参与血红素分解代谢和细胞内铁释放之前血红素血结合蛋白对 MT-1 和 HO-1 基因的调节。血红素结合蛋白系统激活的“氧化还原敏感”转录因子包括c-Jun、RelA/NFκB和MTF-1。特定的铜螯合剂浴铜灵二磺酸盐可防止羰基产生、MTF-1 的核转位以及 MT-1 的诱导，揭示了铜在血红素系统中的新的关键作用。此外，表面氧化还原活性铜是同时调节 HO-1 和 MT-1 的第一个环节，并且是血红素血红素结合蛋白激活氨基末端 c-Jun 激酶 (JNK) 所必需的。
Heme is considered to play an instrumental role in the pathology of hemolysis, trauma, and reperfusion following ischemia. However, data are sparse and experimental models are required. The transport of heme by hemopexin to tissues is a specific, membrane receptor-mediated process. Hemopexin recycles after endocytosis like transferrin. Heme oxygenase-1 (HO-1), transferrin, the transferrin receptor, and ferritin are regulated by heme-hemopexin. Genes that encode proteins important for cellular defenses against oxidative stress, such as the cysteine-rich metallothioneins (MTs), are also activated by hemopexin, as are proteins that regulate cell cycle control including p21WAF1and the tumor suppressor p53. The hemopexin system is being investigated to establish how intracellular events are affected by signal(s) from the plasma membrane due to hemopexin receptor occupancy and heme transport. A transient oxidative modification of proteins, shown by carbonyl production, takes place. Redox processes at the cell surface, which generate cuprous ions, are involved in the regulation of the MT-1 and HO-1 genes by heme-hemopexin before heme catabolism and intracellular release of iron. The “redox-sensitive” transcription factors activated by the hemopexin system include c-Jun, RelA/NFκB and MTF-1. The specific copper chelator bathocuproine disulfonate prevents carbonyl production, the nuclear translocation of MTF-1, and the induction of MT-1 revealing a novel, pivotal role for copper in the hemopexin system. In addition, surface redox-active copper is the first link shown for the concomitant regulation of HO-1 and MT-1 and is required for the activation of the amino-terminal c-Jun kinase (JNK) by heme-hemopexin.
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DOI：
10.1111/j.1432-1033.1993.tb17835.x
发表时间：
1993-05
期刊：
European journal of biochemistry
影响因子：
--
作者：
Kishore K. Srivastava;E. Cable;S. Donohue;Herbert L. Bonkovsky
通讯作者：
Kishore K. Srivastava;E. Cable;S. Donohue;Herbert L. Bonkovsky
影响因子：
15.9
作者：
Kim, KS;Takeda, K;Finkel, T
通讯作者：
Finkel, T
血红素通过血红素结合蛋白转运至肝脏。
DOI：
10.1042/bj1820047
发表时间：
1979
期刊：
The Biochemical journal
影响因子：
--
作者：
A. Smith;W. Morgan
通讯作者：
W. Morgan
DOI：
10.1073/pnas.91.4.1219
发表时间：
1994-02-15
影响因子：
11.1
作者：
PALMITER, RD
通讯作者：
PALMITER, RD
影响因子：
3.7
作者：
A. Smith;J. Eskew;C. Borza;M. Pendrak;R. Hunt
通讯作者：
A. Smith;J. Eskew;C. Borza;M. Pendrak;R. Hunt