Chronic alcohol exposure induces muscle atrophy (myopathy) in zebrafish and alters the expression of microRNAs targeting the Notch pathway in skeletal muscle

Andrew Khayrullin, Lauren Smith, Dhwani Mistry, Amy Dukes, Yu Chin Albert Pan, Mark W Hamrick

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Muscle wasting is estimated to affect 40–60% of alcoholics, and is more common than cirrhosis among chronic alcohol abusers. The molecular and cellular mechanisms underlying alcohol-related musculoskeletal dysfunction are, however, poorly understood. Muscle-specific microRNAs (miRNAs) referred to as myoMirs are now known to play a key role in both myogenesis and muscle atrophy. Yet, no studies have investigated a role for myoMirs in alcohol-related skeletal muscle damage. We developed a zebrafish model of chronic ethanol exposure to better define the mechanisms mediating alcohol-induced muscle atrophy. Adult fish maintained at 0.5% ethanol for eight weeks demonstrated significantly reduced muscle fiber cross-sectional area (∼12%, P < 0.05) compared to fish housed in normal water. Zebrafish miRNA microarray revealed marked changes in several miRNAs with ethanol treatment. Importantly, miR-140, a miRNA that shows 100% sequence homology with miR-140 from both mouse and human, is decreased 10-fold in ethanol treated fish. miR-140 targets several members of the Notch signaling pathway such as DNER, JAG1, and Hey1, and PCR data show that both Hey1 and Notch 1 are significantly up-related (3-fold) in muscle of ethanol treated fish. In addition, miR-146a, which targets the Notch antagonist Numb, is elevated in muscle from ethanol-treated fish. Upregulation of Notch signaling suppresses myogenesis and maintains muscle satellite cell quiescence. These data suggest that miRNAs targeting Notch are likely to play important roles in alcohol-related myopathy. Furthermore, zebrafish may serve as a useful model for better understanding the role of microRNAs in alcohol-related tissue damage.

Original languageEnglish (US)
Pages (from-to)590-595
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume479
Issue number3
DOIs
StatePublished - Oct 21 2016

Fingerprint

Muscular Atrophy
Zebrafish
Muscular Diseases
MicroRNAs
Muscle
Skeletal Muscle
Ethanol
Alcohols
Fishes
Muscles
Fish
Muscle Development
Alcoholics
Sequence Homology
Muscle Cells
Fibrosis
Up-Regulation
Microarrays
Polymerase Chain Reaction
Water

Keywords

  • Myogenesis
  • Satellite cells
  • miR-146a
  • mir-140
  • myoMirs

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chronic alcohol exposure induces muscle atrophy (myopathy) in zebrafish and alters the expression of microRNAs targeting the Notch pathway in skeletal muscle. / Khayrullin, Andrew; Smith, Lauren; Mistry, Dhwani; Dukes, Amy; Pan, Yu Chin Albert; Hamrick, Mark W.

In: Biochemical and Biophysical Research Communications, Vol. 479, No. 3, 21.10.2016, p. 590-595.

Research output: Contribution to journalArticle

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abstract = "Muscle wasting is estimated to affect 40–60{\%} of alcoholics, and is more common than cirrhosis among chronic alcohol abusers. The molecular and cellular mechanisms underlying alcohol-related musculoskeletal dysfunction are, however, poorly understood. Muscle-specific microRNAs (miRNAs) referred to as myoMirs are now known to play a key role in both myogenesis and muscle atrophy. Yet, no studies have investigated a role for myoMirs in alcohol-related skeletal muscle damage. We developed a zebrafish model of chronic ethanol exposure to better define the mechanisms mediating alcohol-induced muscle atrophy. Adult fish maintained at 0.5{\%} ethanol for eight weeks demonstrated significantly reduced muscle fiber cross-sectional area (∼12{\%}, P < 0.05) compared to fish housed in normal water. Zebrafish miRNA microarray revealed marked changes in several miRNAs with ethanol treatment. Importantly, miR-140, a miRNA that shows 100{\%} sequence homology with miR-140 from both mouse and human, is decreased 10-fold in ethanol treated fish. miR-140 targets several members of the Notch signaling pathway such as DNER, JAG1, and Hey1, and PCR data show that both Hey1 and Notch 1 are significantly up-related (3-fold) in muscle of ethanol treated fish. In addition, miR-146a, which targets the Notch antagonist Numb, is elevated in muscle from ethanol-treated fish. Upregulation of Notch signaling suppresses myogenesis and maintains muscle satellite cell quiescence. These data suggest that miRNAs targeting Notch are likely to play important roles in alcohol-related myopathy. Furthermore, zebrafish may serve as a useful model for better understanding the role of microRNAs in alcohol-related tissue damage.",
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