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

18 Citations (Scopus)

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

Fingerprint

Ubiquitin Thiolesterase
Tocopherols
Muscle
Skeletal Muscle
Messenger RNA
Muscles
Proteins
Genes
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Neurodegenerative diseases
Gene encoding
Muscle Relaxation
Muscle Proteins
Hydrolases
Ataxia
Nutrition
Muscle Contraction
Ubiquitin
Transcriptome
Neurodegenerative Diseases

Keywords

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

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sarcolipin and ubiquitin carboxy-terminal hydrolase 1 mRNAs are over-expressed in skeletal muscles of α-tocopherol deficient mice. / Vasu, Vihas T.; Ott, Sean; Hobson, Brad; Rashidi, Vania; Oommen, Saji; Cross, Carroll E; Gohil, Kishorchandra.

In: Free Radical Research, Vol. 43, No. 2, 2009, p. 106-116.

Research output: Contribution to journalArticle

Vasu, Vihas T. ; Ott, Sean ; Hobson, Brad ; Rashidi, Vania ; Oommen, Saji ; Cross, Carroll E ; Gohil, Kishorchandra. / Sarcolipin and ubiquitin carboxy-terminal hydrolase 1 mRNAs are over-expressed in skeletal muscles of α-tocopherol deficient mice. In: Free Radical Research. 2009 ; Vol. 43, No. 2. pp. 106-116.
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AU - Ott, Sean

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AU - Rashidi, Vania

AU - Oommen, Saji

AU - Cross, Carroll E

AU - Gohil, Kishorchandra

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AB - 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.

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