Ascorbate: antioxidant and biochemical activities and their importance for in vitro models.
Ascorbate: antioxidant and biochemical activities and their importance for in vitro models.
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DOI：
10.1007/s00204-021-03167-0
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发表时间：
2021-12
影响因子：
6.1
通讯作者：
Zhitkovich A
中科院分区：
文献类型：
--
作者：
Zhitkovich A
抗坏血酸具有许多生物活性，涉及基因表达、分化和氧化还原动态平衡等基本细胞功能。在生物化学方面，它是控制转录、细胞外基质的形成以及组蛋白和DNA去甲基化的表观遗传过程的双加氧酶大家族(>；60个成员)的辅助因子。抗坏血酸也是一种主要的抗氧化剂，是一种非常有效的初级活性氧的清除剂。抗坏血酸还原Fe(III)对细胞通过DMT1摄取铁很重要。细胞培养模型在毒理学和药理学中被广泛应用于营养素、药物和其他外源物质的机理研究。体外高通量筛选，例如美国的一个大规模Tox21计划，提供了评估大量且数量不断增加的工业化学品的危险性质的机会。然而，典型培养的细胞严重缺乏抗坏血酸，这引发了人们对它们在体内准确概括毒性和其他反应的能力的担忧。抗坏血酸的缺乏和经常不为人所知的使用含有硫醇替代品的培养液改变了细胞在不同方向上的应激敏感性。组织培养中抗坏血酸缺乏的修复可以恢复许多细胞过程的生理状态，它应该会改善目前有限的体外生物测定的毒性预测。
Ascorbate has many biological activities that involve fundamental cellular functions such as gene expression, differentiation, and redox homeostasis. Biochemically, it serves as a cofactor for a large family of dioxygenases (>60 members) which control transcription, formation of extracellular matrix, and epigenetic processes of histone and DNA demethylation. Ascorbate is also a major antioxidant acting as a very effective scavenger of primary reactive oxygen species. Reduction of Fe(III) by ascorbate is important for cellular uptake of iron via DMT1. Cell culture models are extensively used in toxicology and pharmacology for mechanistic studies of nutrients, drugs and other xenobiotics. High-throughput screens in vitro, such as a large-scale Tox21 program in the US, offers opportunities to assess hazardous properties of a vast and growing number of industrial chemicals. However, cells in typical cultures are severely deficient in ascorbate, raising concerns about their ability to accurately recapitulate toxic and other responses in vivo. Scarcity of ascorbate and a frequently unrecognized use of media with its thiol substitute alters stress sensitivity of cells in different directions. Remediation of ascorbate deficiency in tissue culture restores the physiological state of many cellular processes and it should improve a currently limited toxicity predictability of in vitro bioassays.
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影响因子：
6
作者：
Batie M;Druker J;D'Ignazio L;Rocha S
通讯作者：
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影响因子：
64.8
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64.8
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64.5
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影响因子：
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作者：
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通讯作者：
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