AJP - Endo Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 296: E543-E548, 2009. First published January 21, 2009; doi:10.1152/ajpendo.90719.2008
0193-1849/09 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Figures
Right arrow All Versions of this Article:
296/3/E543    most recent
90719.2008v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Li, S.
Right arrow Articles by Lin, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, S.
Right arrow Articles by Lin, J. D.

Regulation of homocysteine homeostasis through the transcriptional coactivator PGC-1{alpha}

Siming Li,1 Erland Arning,3 Chang Liu,1 Victor Vitvitsky,2 Carlos Hernandez,1 Ruma Banerjee,2 Teodoro Bottiglieri,3 and Jiandie D. Lin1

1Life Sciences Institute and Department of Cell and Developmental Biology, 2Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan; and 3Institute of Metabolic Disease, Baylor University Medical Center, Dallas, Texas

Submitted 25 August 2008 ; accepted in final form 12 January 2009

Plasma homocysteine (Hcy) is an independent risk factor for cardiovascular disease. Hcy is a nonprotein amino acid derivative that is generated from the methionine cycle, which provides the methyl group for essentially all biological methylation reactions. Although plasma Hcy levels are elevated in patients with cardiovascular disease, the mechanisms that regulate Hcy homeostasis remain poorly defined. In this study, we found that the expression of key enzymes involved in Hcy metabolism is induced in the liver in response to fasting. This induction coincides with increased expression of peroxisome proliferator-activated receptor-{gamma} coactivator (PGC)-1{alpha}, a transcriptional coactivator that regulates hepatic gluconeogenesis and mitochondrial function. PGC-1{alpha} stimulates the expression of genes involved in Hcy metabolism in cultured primary hepatocytes as well as in the liver. Adenoviral-mediated expression of PGC-1{alpha} in vivo leads to elevated plasma Hcy levels. In contrast, mice deficient in PGC-1{alpha} have lower plasma Hcy concentrations. These results define a novel role for the PGC-1{alpha} coactivator pathway in the regulation of Hcy homeostasis and suggest a potential pathogenic mechanism that contributes to hyperhomocysteinemia.

transcriptional coactivator; peroxisome proliferator-activated receptor-{gamma} coactivator 1{alpha}; homocysteine; liver metabolism; cardiovascular disease


Address for reprint requests and other correspondence: J. D. Lin, 5437 Life Sciences Institute, Univ. of Michigan, 210 Washtenaw Ave., Ann Arbor, MI 48109 (e-mail: jdlin{at}umich.edu)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2009 by the American Physiological Society.