The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme.
The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme.
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DOI：
10.3389/fphys.2016.00594
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发表时间：
2016
影响因子：
4
通讯作者：
Santillo M
中科院分区：
文献类型：
--
作者：
Mondola P;Damiano S;Sasso A;Santillo M
Cu，Zn超氧化物歧化酶（SOD1）是一种普遍存在于细胞内的无碳水化合物二聚体分子，属于清除超氧阴离子的同工酶家族。这种作用当然代表了这种酶的主要和众所周知的功能。在这里，我们强调了SOD1生理学的新方面，指出除了氧自由基酶畸变的重要作用外，该酶还具有一些不可编辑的作用。在过去的二十年中，我们的研究小组在许多细胞系（主要是神经母细胞瘤SK-N-BE细胞）的体外研究中获得了许多数据，表明这种酶要么是组成性分泌的，要么是在高细胞外K+浓度诱导去极化后分泌的。此外，我们提供了许多实验证据，表明SOD1能够通过毒蕈碱M1受体刺激涉及ERK1/2和AKT激活的途径。这些作用伴随着细胞内钙的增加。在本文的最后一部分，我们将介绍突变体SOD1G93A的细胞外分泌缺陷与其在NSC-34细胞内的积累和毒性之间的联系。另外，SOD1G93A的毒性归因于H2O2的Km减少，从而形成OH自由基。有趣的是，SOD1G93A的最后一种非编辑效应可能代表了家族性肌萎缩性侧索硬化症（fALS）发病机制中可能涉及的功能获得。
The Cu,Zn superoxide dismutase (SOD1) is an ubiquitary cytosolic dimeric carbohydrate free molecule, belonging to a family of isoenzymes involved in the scavenger of superoxide anions. This effect certainly represents the main and well known function ascribed to this enzyme. Here we highlight new aspects of SOD1 physiology that point out some inedited effects of this enzyme in addition to the canonic role of oxygen radical enzymatic dismutation. In the last two decades our research group produced many data obtained in in vitro studies performed in many cellular lines, mainly neuroblastoma SK-N-BE cells, indicating that this enzyme is secreted either constitutively or after depolarization induced by high extracellular K+ concentration. In addition, we gave many experimental evidences showing that SOD1 is able to stimulate, through muscarinic M1 receptor, pathways involving ERK1/2, and AKT activation. These effects are accompanied with an intracellular calcium increase. In the last part of this review we describe researches that link deficient extracellular secretion of mutant SOD1G93A to its intracellular accumulation and toxicity in NSC-34 cells. Alternatively, SOD1G93A toxicity has been attributed to a decrease of Km for H2O2 with consequent OH radical formation. Interestingly, this last inedited effect of SOD1G93A could represent a gain of function that could be involved in the pathogenesis of familial Amyotrophic Lateral Sclerosis (fALS).
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影响因子：
9.9
作者：
Alexianu, ME;Kozovska, M;Appel, SH
通讯作者：
Appel, SH
影响因子：
4.7
作者：
Atkin, Julie D.;Farg, Manal A.;Horne, Malcolm K.
通讯作者：
Horne, Malcolm K.
影响因子：
4.8
作者：
Atkin, Julie D.;Farg, Manal A.;Horne, Malcolm K.
通讯作者：
Horne, Malcolm K.
DOI：
10.1097/nen.0b013e318244b635
发表时间：
2012-02
影响因子：
3.2
作者：
Gertz B;Wong M;Martin LJ
通讯作者：
Martin LJ
影响因子：
3.7
作者：
Forsberg K;Jonsson PA;Andersen PM;Bergemalm D;Graffmo KS;Hultdin M;Jacobsson J;Rosquist R;Marklund SL;Brännström T
通讯作者：
Brännström T