Sarcolipin and ubiquitin carboxy-terminal hydrolase 1 mRNAs are over-expressed in skeletal muscles of α-tocopherol deficient mice

Vihas T. Vasu, Sean Ott, Brad Hobson, Vania Rashidi, Saji Oommen, Carroll E Cross, Kishorchandra Gohil

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The transcriptome of ataxic muscles from α-tocopherol transfer protein deficient (ATTP-KO), 23-month old, mice was compared with that of their normal littermates. Genes encoding sarcolipin (sln) and ubiquitin carboxyl-terminal hydrolase (uchl1) were over-expressed (≥10-fold) in ataxic muscles. SLN is a 3.2 kDa membrane protein that binds to sarcoplasmic reticulum calcium ATPase, regulates Ca++ transport and muscle relaxation-contraction cycles. UCHL1 is a 24.8 kDa member of proteosome proteins; it is over-expressed in myofibrillar myopathy and is associated with neurodegenerative diseases. Furthermore, six additional transcripts, three encoding thin-filament proteins and three encoding Ca++ sensing proteins that participate in contraction-relaxation cycle, and eight transcripts that encode members of lysosomal proteins were also over-expressed in ataxic muscles. These observations suggest that chronic α-tocopherol (AT) deficiency activates critical genes of muscle contractility and protein degradation pathways, simultaneously. The magnitude of induction of sln and uchl1 was lower in asymptomatic, 8-month old, ATTP-KO mice and in 8-month old mice fed an AT-depleted diet. These studies suggest sln and uchl1 genes as novel targets of AT deficiency and may offer molecular correlates of well documented descriptions of neuromuscular dysfunctions in AT-deficient rodents. Since the neuromuscular deficits of ATTP-KO mice appear to be similar to those of patients with ATTP mutations, it is suggested that over-expression of sln and uchl1 may also contribute to AT-sensitive ataxia in humans.

Original languageEnglish (US)
Pages (from-to)106-116
Number of pages11
JournalFree Radical Research
Volume43
Issue number2
DOIs
StatePublished - 2009

Keywords

  • Ataxia
  • AVED
  • Calcium homeostasis
  • Muscle relaxation
  • Myopathy
  • Tocopherol transfer protein
  • Ubiquitin
  • Vitamin E

ASJC Scopus subject areas

  • Biochemistry

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