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Journal of Biomedical Optics • Open Access

Binding to and photo-oxidation of cardiolipin by the phthalocyanine photosensitizer Pc 4
Author(s): Myriam E. Rodriguez; Junhwan Kim; Grace B. Delos Santos; Kashif Azizuddin; Jeffrey C. Berlin; Vernon E. Anderson; Malcolm E. Kenney; Nancy L. Oleinick

Paper Abstract

Cardiolipin is a unique phospholipid of the mitochondrial inner membrane. Its peroxidation correlates with release of cytochrome c and induction of apoptosis. The phthalocyanine photosensitizer Pc 4 binds preferentially to the mitochondria and endoplasmic reticulum. Earlier Förster resonance energy transfer studies showed colocalization of Pc 4 and cardiolipin, which suggests cardiolipin as a target of photodynamic therapy (PDT) with Pc 4. Using liposomes as membrane models, we find that Pc 4 binds to cardiolipin-containing liposomes similarly to those that do not contain cardiolipin. Pc 4 binding is also studied in MCF-7c3 cells and those whose cardiolipin content was reduced by treatment with palmitate. Decreased levels of cardiolipin are quantified by thin-layer chromatography. The similar level of binding of Pc 4 to cells, irrespective of palmitate treatment, supports the lack of specificity of Pc 4 binding. Thus, factors other than cardiolipin are likely responsible for the preferential localization of Pc 4 in mitochondria. Nonetheless, cardiolipin within liposomes is readily oxidized by Pc 4 and light, yielding apparently mono- and dihydroperoxidized cardiolipin. If similar products result from exposure of cells to Pc 4-PDT, they could be part of the early events leading to apoptosis following Pc 4-PDT.

Paper Details

Date Published: 1 September 2010
PDF: 10 pages
J. Biomed. Opt. 15(5) 051604 doi: 10.1117/1.3484256
Published in: Journal of Biomedical Optics Volume 15, Issue 5
Show Author Affiliations
Myriam E. Rodriguez, Case Western Reserve Univ. (United States)
Junhwan Kim, Case Western Reserve Univ. (United States)
Grace B. Delos Santos, Case Western Reserve Univ. (United States)
Kashif Azizuddin, Case Western Reserve Univ. (United States)
Jeffrey C. Berlin, Case Western Reserve Univ. (United States)
Vernon E. Anderson, Case Western Reserve Univ. (United States)
Malcolm E. Kenney, Case Western Reserve Univ. (United States)
Nancy L. Oleinick, Case Western Reserve Univ. (United States)

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