Xstrahl in Action: Identification of protein targets for AVM molecular therapies

April 9, 2019

Current treatment methods for arteriovenous malformation (AVM) are surgery and radiosurgery. However, complete occlusion post radiosurgery is achieved within 3 years, while patient remain at risk of haemorrhage. Therefore is important to develop a new molecular targeted treatment for the brain, by identification of membrane proteins that are localised on the AVM endothelium.

In their study “Identification of protein targets in cerebral endothelial cells for brain arteriovenous malformation (AVMs) molecular therapies.” Simonian M, Loo RRO, Rannulu N, Loo JA, Molloy MP, Stoodley MA aim to identify potential protein targets in AVM endothelial cells that discriminate these vessels from normal vessels; these proteins targets were investigated for the molecular therapy of brain AVMs to promote rapid thrombosis after radiosurgery.

They employed in vitro biotinylation that they developed using the Xstrahl CIX3, and mass spectrometry to detect cell surface-exposed proteins in cultures of murine cerebral endothelial cells. Two forms of mass spectrometry were applied (iTRAQ-MS and MSE) to identify and quantify membrane protein expression at various time-points following irradiation which simulates a radiosurgical treatment approach. Immunocytochemistry was used to confirm the expression of selected membrane proteins. ProteinPilot V4.0 software was used to analyse the iTRAQ-MS data and the MSE data was analysed using ProteinLynx Global Server version 2.5 software.

The proteomics data revealed several differentially expressed membrane proteins between irradiated and non-irradiated cells at specific time points, e.g. PECAM-1, cadherin-5, PDI, EPCR and integrins. Immunocytochemistry data confirmed the expression of these proteins.

Cell surface protein biotinylation and proteomics analysis successfully identified membrane proteins from murine brain endothelial cells in response to irradiation. This work suggests potential target protein molecules for evaluation in animal models of brain-AVM.
This Xstrahl In Action was adapted from a article found on a National Library of Medicine website.

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