HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hwang, I. S. S. Articles by Tang, F. Search for Related Content PubMed PubMed Citation Articles by Hwang, I. S. S. Articles by Tang, F.

Age-Related Changes in Adrenomedullin Expression and Hypoxia-Inducible Factor-1 Activity in the Rat Lung and Their Responses to Hypoxia

Departments of ¹ Physiology and ² Anatomy, and ³ the Research Centre of Heart, Brain, Hormone and Healthy Aging, Faculty of Medicine, the University of Hong Kong, Pokfulam, China.

Address correspondence to Fai Tang, PhD, Department of Physiology, Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR. E-mail: ftang{at}hkucc.hku.hk

Male rats aged 3 months, 12 months and 20 months were subjected to breathing 8% oxygen for 6 hours. Lung preproadrenomedullin (AM) messenger RNA (mRNA) levels were measured by solution hybridization-RNase protection assay while AM was measured by radioimmunoassay. The binding of hypoxia-inducible factor-1 (HIF-1) to DNA was determined by electrophoretic mobility shift. There was an age-related increase in basal levels of preproAM mRNA and AM and of the binding of hypoxia-inducible factor (HIF) to DNA. Upon hypoxic stimulation, HIF binding to DNA increased in the young and middle-aged rats, but not in the old rats. AM gene expression increased in response to hypoxia in rats of all ages, but the increase was much less in the old rats. AM peptide levels in the lung decreased with age in hypoxia. In a separate experiment, male rats aged 3 months and 20 months were subjected to hypoxia as described above. PreproAM, calcitonin receptor-like receptor (CRLR), receptor activity modifying protein (RAMP) mRNA, HIF-1 and peptidyl-glycine-amidating monooxygenase (PAM) mRNA levels were measured by reverse transcription–polymerase chain reaction. All except PAM showed a decrease in basal levels and a diminished response to hypoxia in the old rats. Polysome profiling demonstrated decreases in the percentages of translatable preproAM mRNA in response to hypoxia, with a greater decrease in the old than the young rats. It is concluded that an age-dependent decrease in the hypoxic response of the AM system in the lung was associated with high basal levels of HIF activity and AM expression in the old rats, and a lower proportion of translatable preproAM mRNA in the old rats in response to hypoxia. Thus, the HIF-AM pathway may be impaired in the aged lung, and other mechanisms may be present to maintain an AM response to hypoxia.

This article has been cited by other articles:

				A. P. Fernandez, J. Serrano, L. Tessarollo, F. Cuttitta, and A. Martinez Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety, and lower survival under stress conditions PNAS, August 26, 2008; 105(34): 12581 - 12586. [Abstract] [Full Text] [PDF]