title: Impairment of the transcriptional responses to oxidative stress in the heart of aged C57BL/6 mice.
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 transcriptional level, there is an age-related impairment of specific inducible pathways in the response to oxidative stress in the mouse heart.
authors.affiliation: Department of Genetics and Medical Genetics, University of Wisconsin, Madison, 53706, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Edwards
authors.forename: Deepayan
authors.initials: D
authors.lastname: Sarkar
authors.forename: Roger
authors.initials: R
authors.lastname: Klopp
authors.forename: Jason D
authors.initials: JD
authors.lastname: Morrow
authors.forename: Richard
authors.initials: R
authors.lastname: Weindruch
authors.forename: Tomas A
authors.initials: TA
authors.lastname: Prolla
mesh_terms: D000375:Aging; D000818:Animals; D004249:DNA Damage; D007249:Inflammation; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D020033:Protein Isoforms; D011506:Proteins / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D000097642:GADD45 Proteins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010269:Paraquat; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D000097642:GADD45 Proteins