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Hypoxia-inducible factor 1alpha is deregulated by the serum of rats with adjuvant-induced arthritis

Cited 6 time in Web of Science Cited 6 time in Scopus
Authors
Kim, Hye-Lim; Cho, Young-Suk; Choi, Hong; Chun, Yang-Sook; Lee, Zang Hee; Park, Jong-Wan
Issue Date
2009
Publisher
Elsevier
Citation
Biochem Biophys Res Commun. 378 (2009) 123-128
Keywords
AnimalsArthritis, Experimental/*blood/*metabolismDown-RegulationFemaleHypoxia-Inducible Factor 1, alpha Subunit/*biosynthesisProtein BiosynthesisProtein Kinases/metabolismProto-Oncogene Proteins c-akt/antagonists & inhibitorsRatsRats, Inbred LewSerum/*metabolism
Abstract
Rheumatoid arthritis (RA) is known to be associated with increased risks of hypoxia-related diseases, whose progresses are critically determined by HIF-1alpha. The authors hypothesized that the hypoxia-related complications of RA are associated with HIF-1alpha deregulation by some factor(s) in RA serum. Arthritis was induced in female Lewis rats by injecting complete Freund's adjuvant. The effects of arthritic rat serum (ARS) on hypoxic responses were investigated by incubating Hep3B cells in ARS. In the presence of ARS, HIF-1alpha was down-regulated and inactivated under hypoxic conditions. ARS inactivated AKT and mTOR, which led to impaired HIF-1alpha protein synthesis. Furthermore, insulin was found to be deficient in ARS and insulin supplementation fully recovered HIF-1alpha synthesis with AKT and mTOR activation. These results suggest that HIF-1alpha deregulation by components in serum is responsible for the RA-associated aggravation of hypoxic diseases in extra-articular tissues.
ISSN
1090-2104 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19013431

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WBK-4TXDT30-C-9&_cdi=6713&_user=168665&_orig=search&_coverDate=01%2F02%2F2009&_sk=996219998&view=c&wchp=dGLbVlW-zSkzk&md5=695f9929953698461844de8eeb1b1a29&ie=/sdarticle.pdf

http://hdl.handle.net/10371/68153
DOI
https://doi.org/10.1016/j.bbrc.2008.11.013
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
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