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Age-related impairment of the transcriptional responses to oxidative stress in the mouse heart

Age-related impairment of the transcriptional responses to oxidative stress in the mouse heart To investigate the transcriptional response to oxidative stress in the heart and how it changes with age, we examined the cardiac gene expression profiles of young (5-mo-old), middle-aged (15-mo-old), and old (25-mo-old) C57BL/6 mice treated with a single intraperitoneal injection of paraquat (50 mg/kg). Mice were killed at 0, 1, 3, 5, and 7 h after paraquat treatment, and the gene expression profile was obtained with high-density oligonucleotide microarrays. Of 9,977 genes represented on the microarray, 249 transcripts in the young mice, 298 transcripts in the middle-aged mice, and 256 transcripts in the old mice displayed a significant change in mRNA levels (ANOVA, P < 0.01). Among these, a total of 55 transcripts were determined to be paraquat responsive for all age groups. Genes commonly induced in all age groups include those associated with stress, inflammatory, immune, and growth factor responses. Interestingly, only young mice displayed a significant increase in expression of all three isoforms of GADD45, a DNA damage-responsive gene. Additionally, the number of immediate early response genes (IEGs) found to be induced by paraquat was considerably higher in the younger animals. These results demonstrate that, at the transcriptional level, there is an age-related impairment of specific inducible pathways in the response to oxidative stress in the mouse heart. aging; paraquat; gene expression http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Physiological Genomics The American Physiological Society

Age-related impairment of the transcriptional responses to oxidative stress in the mouse heart

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References (54)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
1094-8341
eISSN
1531-2267
DOI
10.1152/physiolgenomics.00172.2002
pmid
12595580
Publisher site
See Article on Publisher Site

Abstract

To investigate the transcriptional response to oxidative stress in the heart and how it changes with age, we examined the cardiac gene expression profiles of young (5-mo-old), middle-aged (15-mo-old), and old (25-mo-old) C57BL/6 mice treated with a single intraperitoneal injection of paraquat (50 mg/kg). Mice were killed at 0, 1, 3, 5, and 7 h after paraquat treatment, and the gene expression profile was obtained with high-density oligonucleotide microarrays. Of 9,977 genes represented on the microarray, 249 transcripts in the young mice, 298 transcripts in the middle-aged mice, and 256 transcripts in the old mice displayed a significant change in mRNA levels (ANOVA, P < 0.01). Among these, a total of 55 transcripts were determined to be paraquat responsive for all age groups. Genes commonly induced in all age groups include those associated with stress, inflammatory, immune, and growth factor responses. Interestingly, only young mice displayed a significant increase in expression of all three isoforms of GADD45, a DNA damage-responsive gene. Additionally, the number of immediate early response genes (IEGs) found to be induced by paraquat was considerably higher in the younger animals. These results demonstrate that, at the transcriptional level, there is an age-related impairment of specific inducible pathways in the response to oxidative stress in the mouse heart. aging; paraquat; gene expression

Journal

Physiological Genomics – The American Physiological Society

Published: Apr 16, 2003

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