Proteome and transcriptome profiling of equine myofibrillar myopathy identifies diminished peroxiredoxin 6 and altered cysteine metabolic pathways

Stephanie J. Valberg, Sudeep Perumbakkam, Erica C. McKenzie, Carrie J Finno

Research output: Contribution to journalArticle

Abstract

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 log2 fold change (FC) in genes involved in sulfur compound/cysteine metabolism such as cystathionine-beta-synthase (CBS, ↓4.51), a cysteine and neutral amino acid membrane transporter (SLC7A10, ↓1.80 MFM), and a cationic transporter (SLC24A1, ↓1.11 MFM). In MFM vs. control at rest, 284 genes were DE with >1 log2 FC in pathways for structure morphogenesis, fiber organization, tissue development, and cell differentiation including > 1 log2 FC in cardiac alpha actin (ACTC1 ↑2.5 MFM), cytoskeletal desmoplakin (DSP ↑2.4 MFM), and basement membrane usherin (USH2A ↓2.9 MFM). Proteome analysis revealed significantly lower antioxidant peroxiredoxin 6 content (PRDX6, ↓4.14 log2 FC MFM), higher fatty acid transport enzyme carnitine palmitoyl transferase (CPT1B, ↑3.49 MFM), and lower sarcomere protein tropomyosin (TPM2, ↓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.

Original languageEnglish (US)
Pages (from-to)1036-1050
Number of pages15
JournalPhysiological Genomics
Volume50
Issue number12
DOIs
StatePublished - Dec 1 2018

Fingerprint

Peroxiredoxin VI
Gene Expression Profiling
Proteome
Metabolic Networks and Pathways
Horses
Cysteine
Desmin
Myofibrillar Myopathy
Muscles
Fatty Acids
Neutral Amino Acid Transport Systems
Antioxidants
Desmoplakins
Cystathionine beta-Synthase
Genes
RNA Sequence Analysis
Sulfur Compounds

Keywords

  • Antioxidant
  • Horse
  • Myopathy
  • Proteome
  • RNA-Seq
  • Transcriptome

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Proteome and transcriptome profiling of equine myofibrillar myopathy identifies diminished peroxiredoxin 6 and altered cysteine metabolic pathways. / Valberg, Stephanie J.; Perumbakkam, Sudeep; McKenzie, Erica C.; Finno, Carrie J.

In: Physiological Genomics, Vol. 50, No. 12, 01.12.2018, p. 1036-1050.

Research output: Contribution to journalArticle

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