Regulation of Apoptotic Endonucleases by EndoG.

Regulation of Apoptotic Endonucleases by EndoG.
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EndoG 对凋亡核酸内切酶的调节。

DOI:
10.1089/dna.2014.2772
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发表时间:
2015
影响因子:
3.1
通讯作者:
Basnakian,AlexeiG
Basnakian,AlexeiG
中科院分区:
生物学4区
文献类型:
--
作者:
Zhdanov,DmitryD;Fahmi,Tariq;Wang,Xiaoying;Apostolov,EugeneO;Sokolov,NikolaiN;Javadov,Sabzali;Basnakian,AlexeiG

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细胞含有几种凋亡内切酶,它们似乎在细胞死亡前后同时起作用,破坏宿主细胞的DNA。这些内切酶是如何被诱导的,以及它们是否可以相互调节,这在很大程度上是未知的。本研究旨在确定凋亡线粒体内切酶G (EndoG)是否可以调节其他凋亡内切酶的表达。研究表明,在肾小管上皮NRK-52E细胞中过表达成熟EndoG可增加caspase-activated DNase (CAD)和DNase I、DNase X、DNase IL2、DNase γ等4种DNase I组内切酶的表达,但不增加DNase 2组内切酶的表达。DNA酶i型内切酶的诱导与内切酶基因启动子/外显子1区域的DNA降解有关。这些结果以及免疫染色内切酶和TUNEL的共定位结果表明,EndoG过表达后的DNA片段除了由EndoG本身引起外,还由DNase I内切酶和CAD引起。总的来说,这些数据首次证明了EndoG调控的凋亡内切酶整体网络的存在。
Cells contain several apoptotic endonucleases, which appear to act simultaneously before and after cell death by destroying the host cell DNA. It is largely unknown how the endonucleases are being induced and whether they can regulate each other. This study was performed to determine whether apoptotic mitochondrial endonuclease G (EndoG) can regulate expression of other apoptotic endonucleases. The study showed that overexpression of mature EndoG in kidney tubular epithelial NRK-52E cells can increase expression of caspase-activated DNase (CAD) and four endonucleases that belong to DNase I group including DNase I, DNase X, DNase IL2, and DNase γ, but not endonucleases of the DNase 2 group. The induction of DNase I-type endonucleases was associated with DNA degradation in promoter/exon 1 regions of the endonuclease genes. These results together with findings on colocalization of immunostained endonucleases and TUNEL suggest that DNA fragmentation after EndoG overexpression was caused by DNase I endonucleases and CAD in addition to EndoG itself. Overall, these data provide first evidence for the existence of the integral network of apoptotic endonucleases regulated by EndoG.
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