Alteration of biochemical and pathological properties of TDP-43 protein by a lipid mediator, 15-deoxy-Δ12,14-prostaglandin J2
Alteration of biochemical and pathological properties of TDP-43 protein by a lipid mediator, 15-deoxy-Δ12,14-prostaglandin J2
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脂质介质 15-脱氧-Δ12,14-前列腺素 J2 改变 TDP-43 蛋白的生化和病理特性
DOI：
10.1016/j.expneurol.2010.01.007
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发表时间：
2010
影响因子：
5.3
通讯作者：
K. Wakabayashi
中科院分区：
文献类型：
--
作者：
Hai;K. Tanji;H. Yoshida;M. Hayakari;T. Shibata;F. Mori;K. Uchida;K. Wakabayashi
TDP-43蛋白病（肌萎缩侧索硬化和额颞叶变性伴泛素阳性包涵体）是一组新分类的神经退行性疾病，其特征在于核TDP-43蛋白在神经元细胞质中的异常积聚和错误定位。15-脱氧-Δ 12，14-前列腺素J2（15 d-PGJ 2）由PGD 2非酶促产生，在炎症和氧化应激反应中发挥作用。事实上，15 d-PGJ 2在肌萎缩侧索硬化症的脊髓运动神经元中上调。在这项研究中，生物化学和免疫细胞化学分析表明，15 d-PGJ 2影响TDP-43的蛋白水解，溶解性和亚细胞定位，类似于TDP-43蛋白病中发现的改变。进一步的研究表明，环戊烯酮环含有亲电碳15 d-PGJ 2可能会影响这些现象。提示15 d-PGJ 2是TDP-43蛋白质病的内源性修饰物。
TDP-43 proteinopathy (amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions) is a newly categorized group of neurodegenerative disorders characterized by abnormal accumulation and mislocalization of nuclear TDP-43 protein in the neuronal cytoplasm. 15-Deoxy-Δ12,14-prostaglandin J2(15d-PGJ2) is non-enzymatically produced from PGD2and plays roles in inflammation and oxidative stress responses. Indeed, 15d-PGJ2is up-regulated in the spinal motor neurons in amyotrophic lateral sclerosis. In this study, biochemical and immunocytochemical analyses showed that 15d-PGJ2affects the proteolysis, solubility, and subcellular localization of TDP-43, similar to alterations found in TDP-43 proteinopathy. Further studies revealed that a cyclopentenone ring containing an electrophilic carbon of 15d-PGJ2is likely to influence these phenomena. These findings suggest that 15d-PGJ2is an endogenous modifier of TDP-43 protein in TDP-43 proteinopathy.
DOI：
10.1097/00005072-199905000-00005
发表时间：
1999-05-01
影响因子：
3.2
作者：
Martin, LJ
通讯作者：
Martin, LJ
DOI：
--
发表时间：
2002-09
期刊：
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
影响因子：
--
作者：
P. A. Campo;Sonali Das;C. Hsiang;T. Bui;C. E. Samuel;D. Straus
通讯作者：
P. A. Campo;Sonali Das;C. Hsiang;T. Bui;C. E. Samuel;D. Straus