Copper Toxicity Is Not Just Oxidative Damage: Zinc Systems and Insight from Wilson Disease.
Copper Toxicity Is Not Just Oxidative Damage: Zinc Systems and Insight from Wilson Disease.
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DOI：
10.3390/biomedicines9030316
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发表时间：
2021-03-20
期刊：
影响因子：
4.7
通讯作者：
Burkhead JL
中科院分区：
文献类型：
--
作者：
Barber RG;Grenier ZA;Burkhead JL
铜、锌等必需金属是多种细胞过程中的重要辅因子，而金属失衡可能会影响或改变疾病状态。铜是有氧生命所必需的，具有重要的氧化还原催化作用。这种氧化还原反应需要精确的细胞内处理和分子到生物水平的动态平衡控制。肝脏作为脊椎动物体内铜稳态的中心器官，长期以来一直与多种铜储存障碍有关，包括肝豆状核变性(WD)(遗传性人类铜中毒)、特发性铜中毒和地方性酪氨酸型婴幼儿肝硬化症。铜失衡也与慢性肝病有关，这些疾病是由肝炎、病毒感染或其他肝脏损伤引起的。铜的不稳定氧化还原特性常被认为是铜中毒的主要机制。然而，主要来自WD模型研究的工作表明，铜毒性可能具有特定的生化后果，而不是直接归因于氧化还原活性。这项工作回顾了铜的毒性，重点放在肝脏，并提出铜的积累特别影响锌依赖的过程。铜中毒具有不完全归因于氧化还原的特定生化影响，这一前景可能会促进对WD和其他铜相关疾病中铜毒性的进一步探讨。
Essential metals such as copper (Cu) and zinc (Zn) are important cofactors in diverse cellular processes, while metal imbalance may impact or be altered by disease state. Cu is essential for aerobic life with significant functions in oxidation-reduction catalysis. This redox reactivity requires precise intracellular handling and molecular-to-organismal levels of homeostatic control. As the central organ of Cu homeostasis in vertebrates, the liver has long been associated with Cu storage disorders including Wilson Disease (WD) (heritable human Cu toxicosis), Idiopathic Copper Toxicosis and Endemic Tyrolean Infantile Cirrhosis. Cu imbalance is also associated with chronic liver diseases that arise from hepatitis viral infection or other liver injury. The labile redox characteristic of Cu is often discussed as a primary mechanism of Cu toxicity. However, work emerging largely from the study of WD models suggests that Cu toxicity may have specific biochemical consequences that are not directly attributable to redox activity. This work reviews Cu toxicity with a focus on the liver and proposes that Cu accumulation specifically impacts Zn-dependent processes. The prospect that Cu toxicity has specific biochemical impacts that are not entirely attributable to redox may promote further inquiry into Cu toxicity in WD and other Cu-associated disorders.
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影响因子：
3.9
作者：
Czachor, JD;Cherian, MG;Koropatnick, J
通讯作者：
Koropatnick, J
影响因子：
25.7
作者：
BAKER, A;GORMALLY, S;MOWAT, AP
通讯作者：
MOWAT, AP
DOI：
10.1111/j.1432-1033.1973.tb02697.x
发表时间：
1973-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BERRY, MN;KUN, E;WERNER, HV
通讯作者：
WERNER, HV
影响因子：
0.9
作者：
Carroll, Liam Stuart;Abdul-Rahim, Azmil H;Murray, Rosanne
通讯作者：
Murray, Rosanne
影响因子：
3.9
作者：
Arain, Salma Aslam;Kazi, Tasneem G.;Panhwar, Abdul Haleem
通讯作者：
Panhwar, Abdul Haleem