Dissociation of mitochondrial depolarization from cytochrome c release during apoptosis induced by photodynamic therapy.

Dissociation of mitochondrial depolarization from cytochrome c release during apoptosis induced by photodynamic therapy.
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DOI:
10.1054/bjoc.2000.1714
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发表时间:
2001-04-20
影响因子:
8.8
通讯作者:
Oleinick NL
Oleinick NL
中科院分区:
医学1区
文献类型:
--
作者:
Chiu SM;Oleinick NL

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酞菁光敏剂Pc 4的光动力学疗法(PDT)诱导小鼠淋巴瘤(LY-R)细胞快速凋亡,起始于线粒体释放细胞色素c。线粒体膜通透性转换孔的开放导致线粒体膜电位(Δ Δ Km)的耗散,这对于细胞色素c从线粒体逃逸到胞质溶胶以及凋亡性细胞死亡是必不可少的。因此,我们评估了PDT后Δ m损失与细胞色素c释放之间的相关性。用300 nM Pc 4和60、90或120 mJ/cm 2红光处理LY-R细胞,导致80-90%的细胞凋亡,并伴有caspase-3样活性在1 h内升高20倍以上。  在所有3个剂量的PDT在这里使用,大部分的细胞色素c从线粒体中释放在照射后15分钟,通过免疫组织化学方法测定。 相比之下,PDT后Δ Δ Tm的损失(通过JC-1或Rh-123的摄取监测)取决于PDT剂量和治疗后时间。尽管细胞色素c在3次给药后15分钟释放,但仅在接受最高剂量PDT的细胞中观察到相应的Δ m损失。 几乎所有接受较低剂量PDT(300 nM Pc 4加60或90 mJ/cm 2)的细胞均保持正常Δ Tm。  因此,我们的结果支持的结论是,细胞色素c的释放从线粒体造成的Pc 4-PDT光损伤是独立的损失的Δ λ m。因此,重要的是要考虑一系列剂量的这种或其他凋亡刺激,在破译的关系,有助于细胞凋亡的代谢反应。© 2001年癌症研究运动http://www.bjcancer.com
Photodynamic therapy (PDT) with the phthalocyanine photosensitizer Pc 4 induces rapid apoptosis in mouse lymphoma (LY-R) cells, initiating with the release of cytochrome c from mitochondria. It has been proposed that the opening of the mitochondrial membrane permeability transition pores, which results in the dissipation of the mitochondrial membrane potential (Δψm), is essential for the escape of cytochrome c from mitochondria into the cytosol as well as for apoptotic cell death. Therefore, we have assessed the correlation between the loss of Δψm and the release of cytochrome c following PDT. Treatment of LY-R cells with 300 nM Pc 4 and 60, 90 or 120 mJ/cm2of red light resulted in apoptosis of 80–90% of the cells, accompanied by >20-fold elevation in caspase-3-like activity within one h. At all 3 doses of PDT employed here, the majority of the cytochrome c was released from mitochondria at 15 min after irradiation, as determined by an immunohistochemical method. In contrast, the loss of Δψm following PDT, as monitored by the uptake of JC-1 or Rh-123, depended on the PDT dose and the post-treatment time. In spite of the release of cytochrome c at 15 min after each of the 3 doses, a corresponding loss of Δψm was observed only for those cells that received the highest dose of PDT. Virtually all cells that received one of the lower doses of PDT (300 nM Pc 4 plus 60 or 90 mJ/cm2) maintained normal Δψm. Hence, our results support the conclusion that the release of cytochrome c from mitochondria resulting from Pc 4-PDT-induced photodamage is independent of the loss of Δψm. Therefore, it is important to consider a range of doses of this or other apoptotic stimuli in deciphering the relationship of metabolic responses that contribute to apoptosis. © 2001 Cancer Research Campaign http://www.bjcancer.com
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发表时间: 1996-10-07
期刊: FEBS LETTERS
影响因子: 3.5
作者:
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期刊: FEBS LETTERS
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期刊: BIOCHIMICA ET BIOPHYSICA ACTA
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发表时间: 1998-10-16
期刊: FEBS LETTERS
影响因子: 3.5
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DOI: 10.1038/34112
发表时间: 1998-01-01
期刊: NATURE
影响因子: 64.8
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