NDLI: Endosomes: guardians against [Ru(Phen)3]2+ photo-action in endothelial cells during in vivo pO2 detection?

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Endosomes: guardians against [Ru(Phen)₃]²⁺ photo-action in endothelial cells during in vivo pO₂ detection?

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Metallomics Vol - 6 Issue - 9

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Endosomes: guardians against [Ru(Phen)₃]²⁺ photo-action in endothelial cells during in vivo pO₂ detection?

Content Provider	Royal Society of Chemistry (RSC)
Author	Miskovsky, Pavol Nichtova, Zuzana Huntosova, Veronika Wagnieres, Georges Novotova, Marta Stroffekova, Katarina
Copyright Year	2014
Abstract	Phototoxicity is a side-effect of in vitro and in vivo oxygen partial pressure (pO2) detection by luminescence lifetime measurement methods. Dichlorotris(1,10-phenanthroline)-ruthenium(II) hydrate ([Ru(Phen)3]2+) is a water soluble pO2 probe associated with low phototoxicity, which we investigated in vivo in the chick's chorioallantoic membrane (CAM) after intravenous or topical administration and in vitro in normal human coronary artery endothelial cells (HCAEC). In vivo, the level of intravenously injected [Ru(Phen)3]2+ decreases within several minutes, whereas the maximum of its biodistribution is observed during the first 2 h after topical application. Both routes are followed by convergence to almost identical “intra/extra-vascular” levels of [Ru(Phen)3]2+. In vitro, we observed that [Ru(Phen)3]2+ enters cells via endocytosis and is then redistributed. None of the studied conditions induced modification of lysosomal or mitochondrial membranes without illumination. No nuclear accumulation was observed. Without illumination [Ru(Phen)3]2+ induces changes in endoplasmic reticulum (ER)-to-Golgi transport. The phototoxic effect of [Ru(Phen)3]2+ leads to more marked ultrastructural changes than administration of [Ru(Phen)3]2+ only (in the dark). These could lead to disruption of Ca2+ homeostasis accompanied by mitochondrial changes or to changes in secretory pathways. In conclusion, we have demonstrated that the intravenous injection of [Ru(Phen)3]2+ into the CAM model mostly leads to extracellular localization of [Ru(Phen)3]2+, while its topical application induces intracellular localization. We have shown in vivo that [Ru(Phen)3]2+ induces minimal photo-damage after illumination with light doses larger by two orders of magnitude than those used for pO2 measurements. This low phototoxicity is due to the fact that [Ru(Phen)3]2+ enters endothelial cells via endocytosis and is then redistributed towards peroxisomes and other endosomal and secretory vesicles before it is eliminated via exocytosis. Cellular response to [Ru(Phen)3]2+, survival or death, depends on its intracellular concentration and oxidation–reduction properties.
Starting Page	2279
Ending Page	2289
Page Count	11
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	6
Issue Number	12
Journal	Metallomics
DOI	10.1039/c4mt00190g
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Oxygen Hydrate Ruthenium Luminescence Homeostasis Redox Coronary circulation Route of administration Exocytosis Endothelium Endocytosis Partial pressure Chorioallantoic membrane Phototoxicity Phenanthroline Endoplasmic reticulum
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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Endosomes: guardians against [Ru(Phen)₃]²⁺ photo-action in endothelial cells during in vivo pO₂ detection?

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