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The role of anti-apoptotic protein kinase Cα in response to hypericin photodynamic therapy in U-87 MG cells

机译:抗凋亡蛋白激酶Cα在U-87 MG细胞对金丝桃素光动力疗法的响应中的作用

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Hypericin photodynamic therapy (HypPDT) has been found to be an efficient inducer of cell death. However, there are indications that HypPDT also activates rescuing pathways. Cell responses to HypPDT are highly dependent on the Hyp intracellular localization and accumulation. We have shown previously that in U87 MG cells Hyp localizes mostly in ER and partially in mitochondria, lysosomes and Golgi, and that HypPDT resulted primarily in apoptosis via the mitochondrial apoptotic pathway. We have also shown that Hyp co-localizes and interacts with anti-apoptotic PKCα in U87 MG cells. To follow up on our previous work, we investigated how HypPDT influences PKCα in U87 MG cells. Here, we show that majority of PKCα present in U87 MG cells is already in a catalytically competent form phosphorylated at Thr638, and it is a likely Bcl2 kinase. The presence of Hyp itself does not affect PKCa distribution. HypPDT acute effect caused PKCα activation and translocation along the plasma membrane and partially in the nuclei. The prolonged effect of HypPDT, 5 and 24 h post PDT, results in PKCα located predominantly in cytosol and nuclei. Moreover, we have shown that phosphorylated catalytically competent PKCα is critical for U87 glioma cell viability in response to HypPDT treatment.
机译:金丝桃素光动力疗法(HypPDT)被发现是有效的细胞死亡诱导剂。但是,有迹象表明,HypPDT也激活了抢救途径。细胞对HypPDT的反应高度依赖于Hyp细胞内的定位和积累。先前我们已经表明,在U87 MG细胞中,Hyp主要位于ER中,部分位于线粒体,溶酶体和高尔基体中,并且HypPDT主要通过线粒体凋亡途径导致细胞凋亡。我们还显示,Hyp在U87 MG细胞中共定位并与抗凋亡PKCα相互作用。为了跟进我们以前的工作,我们研究了HypPDT如何影响U87 MG细胞中的PKCα。在这里,我们显示U87 MG细胞中存在的大多数PKCα已经以在Thr638磷酸化的催化活性形式存在,并且可能是Bcl2激酶。 Hyp本身的存在不会影响PKCa的分布。 HypPDT急性效应导致PKCα活化和沿质膜以及部分在核内移位。 PDT后5和24小时,HypPDT的延长作用导致PKCα主要位于细胞质和细胞核中。此外,我们已经表明,磷酸化的催化活性PKCα对于响应HypPDT治疗的U87胶质瘤细胞活力至关重要。

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