期刊
PHYSIOLOGICAL GENOMICS
卷 50, 期 12, 页码 1036-1050出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/physiolgenomics.00044.2018
关键词
antioxidant; horse; myopathy; proteome; RNA-Seq; transcriptome
资金
- Morris Animal Foundation [D14EQ-021]
- National Institutes of Health [1K01OD-015134, L40 TR-001136]
Equine myofibrillar myopathy (MFM) causes exertional muscle pain and is characterized by myofibrillar disarray and ectopic desmin aggregates of unknown origin. To investigate the pathophysiology of MFM, we compared resting and 3 h postexercise transcriptomes of gluteal muscle and the resting skeletal muscle proteome of MFM and control Arabian horses with RNA sequencing and isobaric tags for relative and absolute quantitation analyses. Three hours after exercise, 191 genes were identified as differentially expressed (DE) in MFM vs. control muscle with >1 log(2) fold change (FC) in genes involved in sulfur compound/cysteine metabolism such as cystathionine-beta-synthase (CBS, down arrow 4.51), a cysteine and neutral amino acid membrane transporter (SLC7A10, down arrow 1.80 MFM), and a cationic transporter (SLC24A1, down arrow 1.11 MFM). In MFM vs. control at rest, 284 genes were DE with >1 log(2) FC in pathways for structure morphogenesis, fiber organization, tissue development, and cell differentiation including >1 log(2) FC in cardiac alpha actin (ACTC1 up arrow 2.5 MFM). cytoskeletal desmoplakin (DSP up arrow 2.4 MFM). and basement membrane usherin (USH2A down arrow 2.9 MFM). Proteome analysis revealed significantly lower antioxidant peroxiredoxin 6 content (PRDX6, down arrow 4.14 log(2) FC MFM), higher fatty acid transport enzyme carnitine palmitoyl transferase (CPT1B, up arrow 3.49 MFM), and lower sarcomere protein tropomyosin (TPM2, down arrow 3.24 MFM) in MFM vs. control muscle at rest. We propose that in MFM horses, altered cysteine metabolism and a deficiency of cysteine-containing antioxidants combined with a high capacity to oxidize fatty acids and generate ROS during aerobic exercise causes chronic oxidation and aggregation of key proteins such as desmin.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据