Dataset Information

Principal component analysis reveals age-related and muscle-type-related differences in protein carbonyl profiles of muscle mitochondria.

ABSTRACT: Carbonyl-modified proteins are considered markers of oxidative damage caused by oxidative stress, aging, and disease. Here we use a previously developed capillary electrophoretic method for detecting femtomole (10(-15) mole) carbonyl levels in mitochondrial proteins that are size separated and profiled. For protein labeling, carbonyls were tagged with Alexa 488 hydrazine and amine groups in proteins with 3-(2-furoyl)quinoline-2-carboxaldehyde. Total mitochondrial protein carbonyl levels were statistically higher in fast- than in slow-twitch muscle of young Fischer 344 rats, and statistically higher in old than in young slow-twitch muscle. Even when some statistical comparisons of the total protein carbonyl levels would not reveal differences, principal component analysis (PCA) classified the carbonyl profiles into four distinct sample groups of different age and muscle types. In addition, PCA was used to predict that most age-related or muscle-type-related changes in carbonyl levels occur in proteins with a molecular weight between 9.8 and 11.7 kD.

SUBMITTER: Feng J

PROVIDER: S-EPMC3038117 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Principal component analysis reveals age-related and muscle-type-related differences in protein carbonyl profiles of muscle mitochondria.

Feng Juan J Navratil Marian M Thompson Ladora V LV Arriaga Edgar A EA

The journals of gerontology. Series A, Biological sciences and medical sciences 20081201 12

Carbonyl-modified proteins are considered markers of oxidative damage caused by oxidative stress, aging, and disease. Here we use a previously developed capillary electrophoretic method for detecting femtomole (10(-15) mole) carbonyl levels in mitochondrial proteins that are size separated and profiled. For protein labeling, carbonyls were tagged with Alexa 488 hydrazine and amine groups in proteins with 3-(2-furoyl)quinoline-2-carboxaldehyde. Total mitochondrial protein carbonyl levels were sta ...[more]

PMID: 19126840

Similar Datasets

Project description:Nearly all human complex traits and diseases exhibit some degree of sex differences, with epigenetics being one of the main contributing factors. Various tissues display sex differences in DNA methylation; however, this has not yet been explored in skeletal muscle, despite skeletal muscle being among the tissues with the most transcriptomic sex differences. For the first time, we investigated the effect of sex on autosomal DNA methylation in human skeletal muscle across three independent cohorts (Gene SMART, FUSION, and GSE38291) using a meta-analysis approach, totalling 369 human muscle samples (222 males and 147 females), and integrated this with known sex-biased transcriptomics. We found 10,240 differentially methylated regions (DMRs) at FDR < 0.005, 94% of which were hypomethylated in males, and gene set enrichment analysis revealed that differentially methylated genes were involved in muscle contraction and substrate metabolism. We then investigated biological factors underlying DNA methylation sex differences and found that circulating hormones were not associated with differential methylation at sex-biased DNA methylation loci; however, these sex-specific loci were enriched for binding sites of hormone-related transcription factors (with top TFs including androgen (AR), estrogen (ESR1), and glucocorticoid (NR3C1) receptors). Fibre type proportions were associated with differential methylation across the genome, as well as across 16% of sex-biased DNA methylation loci (FDR < 0.005). Integration of DNA methylomic results with transcriptomic data from the GTEx database and the FUSION cohort revealed 326 autosomal genes that display sex differences at both the epigenome and transcriptome levels. Importantly, transcriptional sex-biased genes were overrepresented among epigenetic sex-biased genes (p value = 4.6e-13), suggesting differential DNA methylation and gene expression between male and female muscle are functionally linked. Finally, we validated expression of three genes with large effect sizes (FOXO3A, ALDH1A1, and GGT7) in the Gene SMART cohort with qPCR. GGT7, involved in antioxidant metabolism, displays male-biased expression as well as lower methylation in males across the three cohorts. In conclusion, we uncovered 8420 genes that exhibit DNA methylation differences between males and females in human skeletal muscle that may modulate mechanisms controlling muscle metabolism and health.

Dataset Information

Principal component analysis reveals age-related and muscle-type-related differences in protein carbonyl profiles of muscle mitochondria.

Publications

Principal component analysis reveals age-related and muscle-type-related differences in protein carbonyl profiles of muscle mitochondria.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets