Impairment of the transcriptional responses to oxidative stress in the heart of aged C57BL/6 mice

Annals of the New York Academy of Sciences
Michael G EdwardsTomas A Prolla

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 months old), middle-aged (15 months old), and old (25 months 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 hours 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 <.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 genes found to be induced by paraquat was considerably higher in the younger animals. These results demonstrate that, at the trans...Continue Reading

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Citations

Aug 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Enxuan JingC Ronald Kahn
May 25, 2006·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Diane C CabelofAhmad R Heydari
Dec 18, 2007·PLoS Genetics·Jacob M ZahnKevin G Becker
Jun 23, 2012·Mechanisms of Ageing and Development·Pim DekkerAndrea B Maier
Oct 12, 2011·Ageing Research Reviews·Alexey A MoskalevVadim E Fraifeld
Apr 5, 2007·Journal of Molecular and Cellular Cardiology·Jason N PeartGarretta J Gross
Apr 6, 2011·Journal of Neurochemistry·Raquel Bajo-GrañerasMaria D Ganfornina
May 13, 2006·Developmental and Comparative Immunology·Carmen AlvaradoMónica De la Fuente
Oct 27, 2005·Ageing Research Reviews·James E Galvin, Stephen D Ginsberg
May 14, 2016·Circulation Research·Akihiro ShirakabeJunichi Sadoshima
Oct 26, 2012·Cell Cycle·Alexey MoskalevAlexander Zhavoronkov

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