Autophagy role in radiation-induced endothelial surface translocation of mitochondrial protein PDCE2: a novel radiation marker.

Research output: Contribution to conferenceAbstract

Abstract

Background and aims: Combining radiotherapy and vascular targeting for more effective treatment of cancers and brain arteriovenous malformations has been examined in several preclinical studies. Radiation is used as a priming tool to induce significant molecular changes on the endothelial cell surface that are then harnessed as molecular targets for more precise drug delivery. We recently identified the unusual cell surface exposure of the mitochondrial E2 subunit of pyruvate-dehydrogenase complex (PDCE2) in irradiated rat AVM vessels and irradiated mouse cerebral endothelial cells and are exploring the utility of this molecule as a novel and specific radiation-induced vascular target. However, since PDCE2 surface translocation has only previously been associated with the autoimmune disease primary biliary cirrhosis, the novel observation that radiation induces translocation of this mitochondrial protein raises questions about the underlying molecular mechanisms and significance of PDCE2 translocation following radiation exposure. The aim of this study was to examine PDCE2 trafficking in irradiated endothelial cells.
Methods and results: Human brain endothelial cells (hCMEC/D3) were exposed to ionising radiation (0-25 Gy) by linear accelerator and PDCE2 expression studied using immunofluorescent imaging and western blotting. No significant change in total protein expression was observed; however, immunostaining showed that high doses of radiation (15 and 25 Gy) induced cellular hypertrophy associated with a changed expression pattern and localisation of PDCE2. Most notably, irradiated cells demonstrated the presence of large intracellular vesicles enriched with PDCE2. Co-localisation of PDCE2 with LC3B and P62 (autophagy markers) and partially with LAMP-1 (lysosomal marker) suggest a role of autophagy machinery in early PDCE2 translocation. PDCE2 did not significantly co-localise with the exosome marker CD81, the endoplasmic reticulum, or the Golgi.
Conclusions: PDCE2 may provide a novel surface target in irradiated tissues for drug delivery. Translocation from the mitochondria may involve radiation-stimulated induction of autophagy and movement through autophagosomes.
Original languageEnglish
Number of pages1
Publication statusUnpublished - 2019
Event16th International Congress of Radiation Research 2019 - Manchester, United Kingdom
Duration: 25 Aug 201929 Aug 2019
https://confpartners.eventsair.com/QuickEventWebsitePortal/icrr2019/programme/Speaker

Conference

Conference16th International Congress of Radiation Research 2019
CountryUnited Kingdom
CityManchester
Period25/08/1929/08/19
Internet address

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