Valproate and bone loss: ITRAQ proteomics show that valproate reduces collagens and osteonectin in SMA cells

Heidi R. Fuller, Nguyen Thi Man, Le Thanh Lam, Vladimir A. Shamanin, Elliot J. Androphy, Glenn E. Morris

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Valproate is commonly used as an anticonvulsant and mood stabilizer, but its long-term side-effects can include bone loss. As a histone deacetylase (HDAC) inhibitor, valproate has also been considered for treatment of spinal muscular atrophy (SMA). Using iTRAQ labeling technology, followed by two-dimensional liquid chromatography and mass spectrometry analysis, a quantitative comparison of the proteome of an SMA cell line, with and without valproate treatment, was performed. The most striking change was a reduction in collagens I and VI, while over 1000 other proteins remained unchanged. The collagen I alpha-chain precursor was also reduced by more than 50% suggesting that valproate affects collagen I synthesis. The collagen-binding glycoprotein, osteonectin (SPARC, BM-40) was one of the few other proteins that were significantly reduced by valproate treatment. Collagen I is the main protein component of bone matrix and osteonectin has a major role in bone development, so the results suggest a possible molecular mechanism for bone loss following long-term exposure to valproate. SMA patients may already suffer bone weakness as a result of SMN1 gene deletion, so further bone loss would be undesirable.

Original languageEnglish (US)
Pages (from-to)4228-4233
Number of pages6
JournalJournal of Proteome Research
Volume9
Issue number8
DOIs
StatePublished - Aug 6 2010

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Keywords

  • SMN
  • Valproate
  • Valproate and bone loss
  • bone
  • collagen
  • histone deacetylase inhibitor
  • iTRAQ
  • osteonectin
  • spinal muscular atrophy

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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