Author(s): Lukiw WJ, Gordon WC, Rogaev EI, Thompson H, Bazan NG
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Abstract Presenilin-2 (PS2; AD4), a regulator of intercellular signaling during CNS development and cell fate determination, appears to be involved in pathogenic processing of beta-amyloid precursor protein (betaAPP) into potentially neurotoxic beta-amyloid (Abeta) peptides. The PS2 gene promoter contains multiple DNA binding sites for the relatively rare hypoxia-inducible transcription factor HIF-1, suggesting that PS2 expression may be a sensitive indicator of decreased oxygen availability. We have used a cycled hypoxia/hyperoxia (10-50\% O2) protocol followed by normoxia (20\% O2) as a retinal model of retinopathy of prematurity to induce neovascularization (NV) in rat pups. Retinal cell nuclear extracts from pups undergoing hypoxia exhibited a dramatic increase in HIF-1-DNA binding, followed by a delayed (2-7 day) elevation of PS2 RNA message and protein. PS2 gene activation during hypoxia may direct cellular fate towards pathoangiogenesis and intercellular PS2-mediated signaling dysfunction.
This article was published in Neuroreport
and referenced in Journal of Phylogenetics & Evolutionary Biology
- R. K. Pandey
Community oriented integrated ecosystem approach for conservation and sustainable management of forest genetic resources: Challenges in biodiversity conservation in natural tropical forests of India
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