ABCG2 reduces ROS-mediated toxicity and inflammation : A potential role in Alzheimer's disease

Download
  1. Get@NRC: ABCG2 reduces ROS-mediated toxicity and inflammation : A potential role in Alzheimer's disease (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1111/j.1471-4159.2010.06887.x
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titleJournal of Neurochemistry
Volume114
Issue6
Pages15901604; # of pages: 15
SubjectABCG2 up-regulation; Alzheimer�s disease; NF-kB; reactive-oxygen species-mediated toxicity; inflammation
AbstractAlzheimer�s disease is characterized by accumulation and deposition of Aβ peptides in the brain. Aβ deposition generates reactive-oxygen species (ROS), which are involved in Alzheimer�s inflammatory and neurodegenerative pathology. We have previously observed that, in Alzheimer�s disease brain, ABCG2 is up-regulated and AP-1 is activated, but NFkB is not activated. In the present study, we examine the roles and mechanism of ABCG2 on ROS generation, inflammatory gene expression and signaling, heme homeostasis and Aβ production in cell models and on inflammatory signaling and Aβ deposition in Abcg2-knockout and wild-type mice. Our results show that ABCG2 plays a protective role against oxidative stress by decreasing ROS generation, enhancing antioxidant capacity, regulating heme level, and inhibiting inflammatory response in cell models. ABCG2 inhibits NF-kB activation but has less effect on AP-1 activation induced by ROS. This results in inhibition of interleukin-8 and growth-related oncogene (GRO) expression induced by ROS via NF-kB pathway. Abcg2 deficiency increased Ab deposition and NF-kB activation in the brains of Abcg2-knockout mice compared with controls. These findings suggest that ABCG2 may relieve oxidative stress and inflammatory response via inhibiting NF-kB signaling pathway in cell models and brain tissues and thus may play a potential protective role in Alzheimer�s neuroinflammatory response.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedYes
NPARC number17616145
Export citationExport as RIS
Report a correctionReport a correction
Record identifier51206600-e008-4784-aa4a-b611d99a9dc9
Record created2011-03-30
Record modified2016-05-09
Bookmark and share
  • Share this page with Facebook (Opens in a new window)
  • Share this page with Twitter (Opens in a new window)
  • Share this page with Google+ (Opens in a new window)
  • Share this page with Delicious (Opens in a new window)