PMID:17301036

Citation	Hwang, IS, Fung, ML, Liong, EC, Tipoe, GL and Tang, F (2007) Age-related changes in adrenomedullin expression and hypoxia-inducible factor-1 activity in the rat lung and their responses to hypoxia. J. Gerontol. A Biol. Sci. Med. Sci. 62:41-9
Abstract	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-1alpha (HIF-1alpha) 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.
Links	PubMed
Keywords	Adrenomedullin/genetics; Adrenomedullin/metabolism; Aging/genetics; Aging/metabolism; Animals; Anoxia/genetics; Anoxia/metabolism; Anoxia/pathology; Calcitonin Receptor-Like Protein; Disease Models, Animal; Electrophoresis; Gene Expression Regulation, Developmental; Hypoxia-Inducible Factor 1/biosynthesis; Hypoxia-Inducible Factor 1/genetics; Lung/metabolism; Lung/pathology; Male; Mixed Function Oxygenases/genetics; Multienzyme Complexes/genetics; Polyribosomes/metabolism; Protein Precursors/genetics; RNA, Messenger/genetics; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, Calcitonin/genetics; Reverse Transcriptase Polymerase Chain Reaction; Xenopus Proteins
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:ADML	involved_in	GO:0007568: aging	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete

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