Functional role of intracellular labile zinc in pulmonary endothelium.
Functional role of intracellular labile zinc in pulmonary endothelium.
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DOI：
10.4103/2045-8932.105032
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发表时间：
2012-10
影响因子：
2.6
通讯作者：
Pitt BR
中科院分区：
文献类型：
--
作者：
Thambiayya K;Kaynar AM;St Croix CM;Pitt BR
在铁之后，锌是最丰富的必需微量金属。细胞内锌（[Zn]i）通过动态转运、细胞内囊泡储存和与大量蛋白质（估计占人类蛋白质组的3-10%）结合的过程，在广泛的细胞和物种中以严格的配额（100至500 μM）维持。因此，锌是许多金属酶、结构蛋白和转录因子的组成部分。通常认为，[Zn]i的消失的小组分（称为游离或不稳定的锌，并且在操作上被定义为对螯合（通过诸如N，N，N '，N'-四[2-吡啶基甲基]乙二胺[TPEN]的试剂）敏感并且能够通过多种化学和遗传传感器检测的池）参与信号转导途径。锌缺乏症本身可由获得性（营养不良、酒精中毒）或遗传性（影响锌稳态的分子突变，第一个例子是肠病性肢端皮炎）因素引起，或作为各种疾病的组成部分（例如，镰状细胞病、囊性纤维化、败血症）。低锌血症对发育中的人类具有深远的影响，并且生理功能的所有方面（神经元、内分泌、免疫学）都受到影响，尽管关于心血管病理生理学知之甚少。在这篇综述中，我们提供了有关锌稳态的分子和细胞方面的最新知识，然后重点关注肺内皮中锌信号传导的影响，因为它与程序性细胞死亡、收缩力改变以及该部分的脓毒性和无菌性损伤有关。肺。
After iron, zinc is the most abundant essential trace metal. Intracellular zinc ([Zn]i) is maintained across a wide range of cells and species in a tight quota (100 to 500 μM) by a dynamic process of transport, intracellular vesicular storage, and binding to a large number of proteins (estimated at 3-10% of human proteome). As such, zinc is an integral component of numerous metalloenzymes, structural proteins, and transcription factors. It is generally assumed that a vanishingly small component of [Zn]i, referred to as free or labile zinc, and operationally defined as the pool sensitive to chelation (by agents such as N, N, N’, N’-tetrakis [2-pyridylmethyl] ethylenediamine [TPEN]) and capable of detection by a variety of chemical and genetic sensors, participates in signal transduction pathways. Zinc deficiencies, per se, can arise from acquired (malnutrition, alcoholism) or genetic (mutations in molecules affecting zinc homeostasis, the informative and first example being acrodermatitis enteropathica) factors or as a component of various diseases (e.g., sickle cell disease, cystic fibrosis, sepsis). Hypozincemia has profound effects on developing humans, and all facets of physiological function (neuronal, endocrine, immunological) are affected, although considerably less is known regarding cardiovascular pathophysiology. In this review, we provide an update on current knowledge of molecular and cellular aspects of zinc homeostasis and then focus on implications of zinc signaling in pulmonary endothelium as it relates to programmed cell death, altered contractility, and septic and aseptic injury to this segment of the lung.