NDLI: Comparative kinetics of damage to the plasma and mitochondrial membranes by intra-cellularly synthesized and externally-provided photosensitizers using multi-color FACS.

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Comparative kinetics of damage to the plasma and mitochondrial membranes by intra-cellularly synthesized and externally-provided photosensitizers using multi-color FACS.

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Comparative kinetics of damage to the plasma and mitochondrial membranes by intra-cellularly synthesized and externally-provided photosensitizers using multi-color FACS.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Haupt, Sara Malik, Zvi Ehrenberg, Benjamin
Description	Country affiliation: Israel Author Affiliation: Haupt S ( Department of Physics and Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel.)
Abstract	Photodynamic therapy (PDT) of cancer involves inflicting lethal damage to the cells of malignant tumors, primarily by singlet oxygen that is generated following light-absorption in a photosensitizer molecule. Dysfunction of cells is manifested in many ways, including peroxidation of cellular components, membrane rupture, depolarization of electric potentials, termination of mitochondrial activity, onset of apoptosis and necrosis and eventually cell lysis. These events do not necessarily occur in linear fashion and different types of damage to cell components occur, most probably, in parallel. In this report we measured the relative rates of damage to two cellular membranes: the plasma membrane and the mitochondrial membrane. We employed photosensitizers of diverse hydrophobicities and used different incubation procedures, which lead to their different intra-cellular localizations. We monitored the damage that was inflicted on these membranes, by employing optical probes of membrane integrity, in a multi-color FACS experiment. The potentiometric indicator JC-1 monitored the electric cross-membrane potential of the mitochondria and the fluorometric indicator Draq7 monitored the rupture of the plasma membrane. We show that the electric depolarization of the mitochondrial membrane and the damage to the enveloping plasma membrane proceed with different kinetics that reflect the molecular character and intracellular location of the sensitizer: PpIX that is synthesized in the cells from ALA causes rapid mitochondrial damage and very slow damage to the plasma membrane, while externally added PpIX has an opposite effect. The hydrophilic sensitizer HypS4 can be taken up by the cells by different incubation conditions, and these affect its intracellular location, and as a consequence either the plasma membrane or the mitochondria is damaged first. A similar correlation was found for additional extracellularly-provided photosensitizers HP and PpIX.
File Format	HTM / HTML
ISSN	1474905X
Issue Number	1
Volume Number	13
e-ISSN	14749092
Journal	Photochemical & Photobiological Sciences
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2014-01-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Chemistry Discipline Biology Aminolevulinic Acid Pharmacology Cell Membrane Drug Effects Membrane Potential, Mitochondrial Mitochondrial Membranes Photosensitizing Agents Protoporphyrins Anthracyclines Benzimidazoles Carbocyanines Cell Line, Tumor Cell Survival Flow Cytometry Fluorescent Dyes Humans Hydrophobic And Hydrophilic Interactions Kinetics Light Neurons Pathology Comparative Study Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry

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