Initiation of apoptosis and autophagy by photodynamic therapy
Initiation of apoptosis and autophagy by photodynamic therapy
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DOI：
10.1002/lsm.20334
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发表时间：
2006-06-01
影响因子：
2.4
通讯作者：
Reiners, John J., Jr.
中科院分区：
文献类型：
--
作者：
Kessel, David;Vicente, M. Graca H.;Reiners, John J., Jr.
背景和目的：本研究旨在探讨光动力疗法(PDT)后细胞死亡的方式。研究设计：检测光动力疗法(PDT)诱导内质网(ER)光损伤后小鼠白血病L1210细胞和人前列腺Bax缺陷DU145细胞。用相差显微镜、荧光显微镜和电子显微镜观察细胞形态的变化、染色质凝集、线粒体膜电位丧失和吞噬酶体的形成。Western blotting用于评估自噬标记Lc3-I到Lc3-II的过程。结果：L1210细胞在内质网光损伤后均发生了细胞凋亡和自噬，24小时后以自噬为主。在DU145细胞中，导致类似细胞毒性的PDT条件只启动了自噬。PI3-激酶抑制剂抑制L1210细胞的自噬作用，表现为抑制空泡化和LC3加工。结论：L1210细胞在内质网光损伤后发生自噬和凋亡。在Bax基因缺失的DU145细胞系中，仅观察到自噬。目前的信息表明，自噬既可以作为生存途径，也可以作为死亡途径。我们认为，在光动力疗法的背景下，这也可能是正确的。
Background and Objectives: This study was designed to examine modes of cell death after photodynamic therapy (PDT).Study Design: Murine leukemia L1210 cells and human prostate Bax-deficient DU145 cells were examined after PDT-induced photodamage to the endoplasmic reticulum (ER). Phase contrast, fluorescence and electron microscopy were used to identify changes in cellular morphology, chromatin condensation, loss of mitochondrial membrane potential, and formation of phagolysosomes. Western blots were used to assess the processing of LC3-I to LC3-II, a marker for autophagy. Inhibitors of apoptosis and/or autophagy were used to delineate the contributions of the two pathways to the effects of PDT.Results: Both apoptosis and autophagy occurred in L1210 after ER photodamage with the latter predominating after 24 hours. In DU145 cells, PDT conditions causing comparable cytotoxicity only initiated autophagy. PI3-kinase inhibitors suppressed autophagy in both cell lines as indicated by inhibition of vacuolization and LC3 processing.Conclusions: Both autophagy and apoptosis were observed in L1210 cells following ER photodamage. In the Bax-deficient DU145 cell line only autophagy was observed. Current information suggests that autophagy can function as either a survival or death pathway. We propose that in the context of PDT, this may also be true.