SOD1 Lysine 123 Acetylation in the Adult Central Nervous System.
SOD1 Lysine 123 Acetylation in the Adult Central Nervous System.
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DOI：
10.3389/fncel.2016.00287
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发表时间：
2016
影响因子：
5.3
通讯作者：
Bossy-Wetzel E
中科院分区：
文献类型：
--
作者：
Kaliszewski M;Kennedy AK;Blaes SL;Shaffer RS;Knott AB;Song W;Hauser HA;Bossy B;Huang TT;Bossy-Wetzel E
超氧化物歧化酶1（SOD 1）基因敲除（SOD 1 −/−）小鼠表现出加速老化表型。在人类中，SOD 1突变与家族性肌萎缩侧索硬化症（ALS）有关，野生型SOD 1的翻译后修饰（PTM）与散发性ALS有关。可逆乙酰化调节许多酶，蛋白质组学研究已经确定SOD 1在赖氨酸123（K123）处乙酰化。K123-乙酰化SOD 1（Ac-K123 SOD 1）在神经系统中的功能和分布尚不清楚。在这里，我们产生了针对Ac-K123 SOD 1的多克隆兔抗体。Sod 1 −/−小鼠中的Sod 1缺失、K123突变或Ac-K123肽预吸收均消除了抗体结合。使用免疫组织化学，我们评估了Ac-K123 SOD 1在正常成年小鼠神经系统中的分布。在小脑，Ac-K123 SOD 1染色是突出的颗粒细胞层（GCL）和浦肯野细胞树突和中间神经元的分子细胞层的细胞体。在海马，Ac-K123 SOD 1染色在海马伞，下托，锥体细胞和Schaffer侧支纤维的角氨场1（CA 1）区域和颗粒和神经元祖细胞的齿状回是强的。此外，在脉络丛（CP）和脑室室管膜和脊髓中央管中观察到标记。在嗅球中，Ac-K123 SOD 1染色在感觉神经元的轴突、中间神经元的细胞体以及僧帽细胞和簇状细胞的神经突中突出。在视网膜中，标记在视网膜神经节细胞层（RGCL）和视网膜神经节细胞（RGCs）的轴突、内核层（INL）和外核层（ONL）的视锥光感受器中是强的。总之，我们的研究结果描述了Ac-K123 SOD 1分布到正常神经系统的不同区域和细胞类型。
Superoxide dismutase 1 (SOD1) knockout (Sod1−/−) mice exhibit an accelerated aging phenotype. In humans, SOD1 mutations are linked to familial amyotrophic lateral sclerosis (ALS), and post-translational modification (PTM) of wild-type SOD1 has been associated with sporadic ALS. Reversible acetylation regulates many enzymes and proteomic studies have identified SOD1 acetylation at lysine 123 (K123). The function and distribution of K123-acetylated SOD1 (Ac-K123 SOD1) in the nervous system is unknown. Here, we generated polyclonal rabbit antibodies against Ac-K123 SOD1. Sod1 deletion in Sod1−/− mice, K123 mutation or preabsorption with Ac-K123 peptide all abolished antibody binding. Using immunohistochemistry, we assessed Ac-K123 SOD1 distribution in the normal adult mouse nervous system. In the cerebellum, Ac-K123 SOD1 staining was prominent in cell bodies of the granular cell layer (GCL) and Purkinje cell dendrites and interneurons of the molecular cell layer. In the hippocampus, Ac-K123 SOD1 staining was strong in the fimbria, subiculum, pyramidal cells and Schaffer collateral fibers of the cornus ammonis field 1 (CA1) region and granule and neuronal progenitor cells of the dentate gyrus. In addition, labeling was observed in the choroid plexus (CP) and the ependyma of the brain ventricles and central canal of the spinal cord. In the olfactory bulb, Ac-K123 SOD1 staining was prominent in axons of sensory neurons, in cell bodies of interneurons and neurites of the mitral and tufted cells. In the retina, labeling was strong in the retinal ganglion cell layer (RGCL) and axons of retinal ganglion cells (RGCs), the inner nuclear layer (INL) and cone photoreceptors of the outer nuclear layer (ONL). In summary, our findings describe Ac-K123 SOD1 distribution to distinct regions and cell types of the normal nervous system.
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影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
2.5
作者：
Brown, JP;Couillard-Després, S;Kuhn, HG
通讯作者：
Kuhn, HG
影响因子：
7.4
作者：
Behndig, A;Karlsson, K;Marklund, SL
通讯作者：
Marklund, SL
影响因子：
5.3
作者：
Knapp, LT;Klann, E
通讯作者：
Klann, E
影响因子：
4.8
作者：
Antinone, Sarah E.;Ghadge, Ghanashyam D.;Green, William N.
通讯作者：
Green, William N.