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

被引:90
作者
Chiu, SM
Oleinick, NL [1 ]
机构
[1] Case Western Reserve Univ, Sch Med, Dept Radiat Oncol, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Sch Med, CWRU Ireland Comprehens Canc Ctr, Cleveland, OH 44106 USA
关键词
photodynamic therapy; phthalocyanine Pc 4; mitochondria; apoptosis; membrane potential; cytochrome c;
D O I
10.1054/bjoc.2000.1714
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 (Delta psi (m),), 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 Delta psi (m) and the release of cytochrome c following PDT Treatment of LY-R cells with 300 nM Pc 4 and 60, 90 or 120 mJ/cm(2) of 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 Delta psi (m) 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 Delta psi (m) 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/cm(2)) maintained normal Delta psi (m). 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 Delta psi (m),. 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. (C) 2001 Cancer Research Campaign.
引用
收藏
页码:1099 / 1106
页数:8
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