AJP - Regu AJP: Lung Cellular and Molecular Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Regul Integr Comp Physiol 297: R158-R165, 2009. First published May 6, 2009; doi:10.1152/ajpregu.90829.2008
0363-6119/09 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
297/1/R158    most recent
90829.2008v1
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 PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Ndubuizu, O. I.
Right arrow Articles by LaManna, J. C.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ndubuizu, O. I.
Right arrow Articles by LaManna, J. C.

ARTICLES

Increased prolyl 4-hydroxylase expression and differential regulation of hypoxia-inducible factors in the aged rat brain

Obinna I. Ndubuizu,1 Juan C. Chavez,2 and Joseph C. LaManna1

1Department of Physiology & Biophysics, Case Western Reserve University, Cleveland, Ohio; and 2Discovery Translational Medicine, Wyeth Research, Collegeville, Pennsylvania

Submitted 10 October 2008 ; accepted in final form 29 April 2009

Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors that mediate the adaptive response of mammalian cells and tissues to changes in tissue oxygenation. In the present study, we show an age-dependent decline in cortical HIF-1{alpha} accumulation and activation of HIF target genes in response to hypoxia. This inducible response is significantly attenuated in the cerebral cortex of 18-mo-old Fischer 344 rat yet virtually absent in the cerebral cortex of 24-mo-old Fischer 344 rat. This attenuated HIF-1{alpha} response had no effect on mRNA upregulation of HIF-independent genes in the aged cortex. We have provided evidence that this absent HIF-1{alpha} response is directly correlated with an increase in the expression of the HIF regulatory enzyme, prolyl 4-hydroxylase (PHD). In addition, our study shows that cortical HIF-2{alpha} expression in senescent normoxic controls is also significantly greater than that of younger normoxic controls, despite no difference in HIF-2{alpha} mRNA levels. The posttranslational regulation of HIF-2{alpha} under normoxic conditions seems to be attenuated in the aged rat brain, which is an in vivo demonstration of differential regulation of HIF-1{alpha} and HIF-2{alpha}.

aging; hypoxia; hypoxia inducible factor-1; hypoxia inducible factor-2


Address for reprint requests and other correspondence: J. C. LaManna, Dept. of Physiology & Biophysics, Case Western Reserve Univ., School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106-4938 (e-mail: joseph.lamanna{at}case.edu)






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