Redox response of the endogenous calcineurin inhibitor Adapt 78.
Redox response of the endogenous calcineurin inhibitor Adapt 78.
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内源性钙调神经磷酸酶抑制剂 Adapt 78 的氧化还原反应。
DOI：
10.1016/j.freeradbiomed.2005.03.036
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Crawford,DanaR
中科院分区：
文献类型：
--
作者：
Narayan,AnanthV;Stadel,Rebecca;Hahn,AmyB;Bhoiwala,DiptiL;Cornielle,Geysha;Sarazin,Erwin;Koleilat,Issam;Crawford,DanaR
Adapt78(DSCR1/calpressin/MCIP1)是钙调神经磷酸酶的天然抑制物，钙调神经磷酸酶是一种重要的细胞内磷酸酶，介导许多细胞对钙的反应。我们之前报道了Adapt78的两个主要胞浆亚型(1和4)，而亚型4是一种氧化和钙应激反应蛋白。使用更高的细胞培养密度和新的抗体，我们再次观察到这两种主要异构体都定位于胞浆，但在细胞核中也检测到显著水平的异构体4(而不是异构体1)，它存在于不溶性区域，与RNA无关。细胞暴露于过氧化氢后，胞浆内异构体4的定位略有增加，胞核中的异构体4显著减少。氧化应激引起的异构体4磷酸化状态的改变，其特征是较少的(低)磷酸化的Adapt78的丢失，尽管一般的Adapt78的降解是由蛋白质体介导的，但并不是由于加速降解。最后，Jurkat的刺激和初级T淋巴细胞信号导致了异构体4的诱导。这种诱导是BAPTA、二苯碘和N-乙酰半胱氨酸可抑制的，并伴随着经典免疫反应介质和钙调神经磷酸酶途径刺激的白介素2的诱导。这些研究揭示了Adapt78亚型4的新的氧化还原相关活性，这可能与其已知的钙调神经磷酸酶调节和细胞保护活性有关，并进一步表明Adapt78在基本T细胞反应中发挥作用。
Adapt78 (DSCR1/calcipressin/MCIP1) is a potent natural inhibitor of calcineurin, an important intracellular phosphatase that mediates many cellular responses to calcium. We previously reported two major cytosolic isoforms (1 and 4) of Adapt78, and that isoform 4 is an oxidative and calcium stress-response protein. Using a higher cell culture density and new antibody, we again observed that both major isoforms localized to the cytosol, but a significant level of isoform 4 (but not isoform 1) was also detected in the nucleus where it was present in the nonsoluble region and not associated with RNA. Exposure of cells to hydrogen peroxide led to the significant loss of isoform 4 from the nucleus with a moderate increase in cytosolic localization. The change in isoform 4 phosphorylation state in response to oxidative stress, characterized by a loss of the lesser (hypo) phosphorylated Adapt78, was not due to accelerated degradation, although general Adapt78 degradation was proteosome mediated. Finally, stimulation of Jurkat and primary T-lymphocyte signaling led to isoform 4 induction. This induction was BAPTA, diphenylene iodonium, and N-acetylcysteine inhibitable, and accompanied by induction of the classic immune response mediator and calcineurin-pathway-stimulated interleukin-2. These studies reveal new redox-related activities for Adapt78 isoform 4, which may contribute to its known calcineurin-regulating and cytoprotective activities, and further suggest that Adapt78 plays a role in basic T-cell response.
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影响因子：
11.4
作者：
Görlach, J;Fox, DS;Heitman, J
通讯作者：
Heitman, J
影响因子：
3.9
作者：
Leahy, KP;Crawford, DR
通讯作者：
Crawford, DR
DOI：
10.1046/j.1432-1327.2000.01240.x
发表时间：
2000-04
期刊：
European journal of biochemistry
影响因子：
--
作者：
Debbie Sommer;K. L. Fakata;S. Swanson;Paul M. Stemmer
通讯作者：
Debbie Sommer;K. L. Fakata;S. Swanson;Paul M. Stemmer
Adapt78 家族的多个氧化应激反应成员。
影响因子：
7.4
作者：
Michtalik,HenryJ;Narayan,AnanthV;Bhatt,Nishant;Lin,HY;Mulligan,MichaelT;Zhang,ShenLi;Crawford,DanaR
通讯作者：
Crawford,DanaR
影响因子：
3.9
作者：
WIESE, AG;PACIFICI, RE;DAVIES, KJA
通讯作者：
DAVIES, KJA