Ionizing radiation reduces ADAM10 expression in brain microvascular endothelial cells undergoing stress-induced senescence
By L. McRobb, M. McKay, J. Gamble, Michael Grace, V. Moutrie, E. D. Santos, V. Lee, Zhenjun Zhao, M. Molloy, M. Stoodley. 2017
39 citations recorded by the source corpus.
Cellular senescence is associated with aging and is considered a potential contributor to age-associated neurodegenerative disease. Exposure to ionizing radiation increases the risk of developing premature neurovascular degeneration and dementia but also induces premature senescence. As cells of the cerebrovascular endothelium are particularly susceptible to radiation and play an important role in brain homeostasis, we investigated radiation-induced senescence in brain microvascular endothelial cells (EC). Using biotinylation to label surface proteins, streptavidin enrichment and proteomic analysis, we analyzed the surface proteome of stress-induced senescent EC in culture. An array of both recognized and novel senescence-associated proteins were identified. Most notably, we identified and validated the novel radiation-stimulated down-regulation of the protease, a disintegrin and metalloprotease 10 (ADAM10). ADAM10 is an important modulator of amyloid beta protein production, accumulation of which is central to the pathologies of Alzheimer's disease and cerebral amyloid angiopathy. Concurrently, we identified and validated increased surface expression of ADAM10 proteolytic targets with roles in neural proliferation and survival, inflammation and immune activation (L1CAM, NEO1, NEST, TLR2, DDX58). ADAM10 may be a key molecule linking radiation, senescence and endothelial dysfunction with increased risk of premature neurodegenerative diseases normally associated with aging.
Subfields: Neurology, Physiology
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In Physiology
Citations in the corpus
- A Disintegrin and Metalloproteinase (ADAM) and ADAM with Thrombospondin Motifs (ADAMTS) Family in Vascular Biology and Disease (2019, background): “Conversely, some studies suggest that ADAM-10 may be associated with vascular cell survival as ionizing radiation reduces ADAM-10 expression and induces neurovascular cell senescence and death [139].”