alexa Cyclooxygenase-2 and presenilin-1 gene expression induced by interleukin-1beta and amyloid beta 42 peptide is potentiated by hypoxia in primary human neural cells.


Journal of Alzheimers Disease & Parkinsonism

Author(s): Bazan NG, Lukiw WJ

Abstract Share this page

Abstract Lipid messengers and amyloid beta (Abeta) peptides generated by cyclooxygenase-2 (COX-2) and presenilin-1 (PS1) mediate pro-inflammatory signaling and neural degeneration in Alzheimer's disease (AD) brain. This study provides data showing that the COX-2 and PS1 genes each transcribe rare, highly labile RNA species that display early response gene behavior in human neural (HN) cells in primary culture, down-regulation during human neural development, and up-regulation in AD neocortex and hippocampal CA1. Together, interleukin-1beta and amyloid beta42 peptide [IL-1beta+Abeta42] synergistically activated COX-2 and PS1 gene expression preceded by increases in AP1-, STAT1alpha-, and in particular NF-kappaBp50/p65- and HIF-1alpha-DNA binding. These events were markedly potentiated by hypoxia and blocked by the antioxidant alpha-phenyl-N-tert-butyl nitrone. Broad transcription profiling further indicated that hypoxia-induced, [IL-1beta+Abeta42]-treated HN cells display robust induction of COX-2 and PS1 as well as a pro-inflammatory gene family that includes NF-kappaBp50/p105, IL-1beta precursor, and cytosolic phospholipase A2 genes. These findings indicate a novel [IL-1beta+Abeta42]-mediated, hypoxia-enhanced, free radical-triggered gene program that drives inflammatory gene signaling and suggest a mechanism by which hypoxia during aging contributes episodically to amyloidogenesis, inflammation, and AD pathophysiology. This article was published in J Biol Chem and referenced in Journal of Alzheimers Disease & Parkinsonism

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version