Binding to and photo-oxidation of cardiolipin by the phthalocyanine photosensitizer Pc 4.
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.
Case Western Reserve University, Department of Radiation Oncology, Cleveland, Ohio 44106-4942, USA.
Myriam E
ME
Rodriguez
Junhwan
J
Kim
Grace B
GB
Delos Santos
Kashif
K
Azizuddin
Jeffrey
J
Berlin
Vernon E
VE
Anderson
Malcolm E
ME
Kenney
Nancy L
NL
Oleinick
D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002308:Cardiolipins / Q000737:chemistry* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism*; D008081:Liposomes; D053078:Membrane Potential, Mitochondrial; D051336:Mitochondrial Membranes / Q000378:metabolism; D010084:Oxidation-Reduction; D010168:Palmitates / Q000494:pharmacology; D055668:Photochemical Processes; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000378:metabolism*
D002308:Cardiolipins; D007211:Indoles; D008081:Liposomes; D010168:Palmitates; D017319:Photosensitizing Agents; C107448:phthalocyanine Pc 4