The familial Parkinson's disease gene DJ-1 (PARK7) is expressed in red cells and plays a role in protection against oxidative damage.
The familial Parkinson's disease gene DJ-1 (PARK7) is expressed in red cells and plays a role in protection against oxidative damage.
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DOI：
10.1016/j.bcmd.2010.07.014
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发表时间：
2010-10-15
影响因子：
2.3
通讯作者：
Friedman, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Xu, Xiuling;Martin, Florent;Friedman, Jeffrey S.
抗氧化酶锰超氧化物歧化酶（SOD 2）是对抗线粒体超氧化物的主要防御。鼠造血细胞中受损的SOD 2活性影响红细胞发育，导致以线粒体内铁沉积、网织红细胞增多和红细胞寿命缩短为特征的贫血。正常和SOD 2缺陷型成红细胞的基因表达谱鉴定了帕金森病基因座DJ-1（Park 7）作为差异表达的转录本。为了研究DJ-1在造血细胞发育中的作用和对由Sod 2损失引起的氧化应激的保护，我们评估了DJ-1敲除动物和在由胎肝移植产生的造血细胞中缺乏SOD 2和DJ-1的嵌合动物的红细胞参数、网织红细胞计数、红细胞周转率和活性氧产生。我们还研究了DJ-1蛋白在原代小鼠红系和红白血病细胞（MEL）中的表达。DJ-1的缺失加剧了SOD 2缺乏的表型，增加了网织红细胞计数并降低了红细胞存活率。使用MEL细胞，我们发现DJ-1在红系分化过程中在蛋白水平上上调。这些结果表明，DJ-1在保护红系细胞免受氧化损伤中起生理作用，这是在氧化应激的背景下揭示的功能。
The antioxidant enzyme manganese superoxide dismutase (SOD2) serves as the primary defense against mitochondrial superoxide. Impaired SOD2 activity in murine hematopoietic cells affects erythroid development, resulting in anemia characterized by intra-mitochondrial iron deposition, reticulocytosis and shortened red cell life span. Gene expression profiling of normal and SOD2 deficient erythroblasts identified the Parkinson’s disease locus DJ-1 (Park7) as a differentially expressed transcript. To investigate the role of DJ-1 in hematopoietic cell development and protection against oxidative stress caused by Sod2 loss, we evaluated red cell parameters, reticulocyte count, red cell turnover and reactive oxygen species production in DJ-1 knockout animals and chimeric animals lacking both SOD2 and DJ-1 in hematopoietic cells generated by fetal liver transplantation. We also investigated DJ-1 protein expression in primary murine erythroid and erythroleukemia cells (MEL). Loss of DJ-1 exacerbates the phenotype of SOD2 deficiency, increasing reticulocyte count and decreasing red cell survival. Using MEL cells, we show that DJ-1 is up-regulated at protein level during erythroid differentiation. These results indicate that DJ-1 plays a physiologic role in protection of erythroid cells from oxidant damage, a function unmasked in the context of oxidative stress.
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影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
DOI：
10.1073/pnas.0607260103
发表时间：
2006-10-10
影响因子：
11.1
作者：
Clements, Casey M.;McNally, Richard S.;Ting, Jenny P-Y.
通讯作者：
Ting, Jenny P-Y.
影响因子：
4.4
作者：
Duan, Xunbao;Kelsen, Steven G.;Merali, Salim
通讯作者：
Merali, Salim
影响因子：
20.3
作者：
Friedman, JS;Lopez, MF;Burakoff, SJ
通讯作者：
Burakoff, SJ
影响因子：
15.3
作者：
Friedman, J S;Rebel, V I;Derby, R;Bell, K;Huang, T T;Kuypers, F A;Epstein, C J;Burakoff, S J
通讯作者：
Burakoff, S J