Proteomic and metabolomic analysis of H2O2-induced premature senescent human mesenchymal stem cells

Ji Soo Kim, Eui Jin Kim, Hyun Jung Kim, Ji Young Yang, Geum Sook Hwang, Chan Wha Kim

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Stress induced premature senescence (SIPS) occurs after exposure to many different sublethal stresses including H2O2, hyperoxia, or tert-butylhydroperoxide. Human mesenchymal stem cells (hMSCs) exhibit limited proliferative potential in vitro, the so-called Hayflick limit. According to the free-radical theory, reactive oxygen species (ROS) might be the candidates responsible for senescence and age-related diseases. H2O2 may be responsible for the production of high levels of ROS, in which the redox balance is disturbed and the cells shift into a state of oxidative stress, which subsequently leads to premature senescence with shortening telomeres. H2O2 has been the most commonly used inducer of SIPS, which shares features of replicative senescence (RS) including a similar morphology, senescence-associated β-galactosidase activity, cell cycle regulation, etc. Therefore, in this study, the senescence of hMSC during SIPS was confirmed using a range of different analytical methods. In addition, we determined five differentially expressed spots in the 2-DE map, which were identified as Annexin A2 (ANXA2), myosin light chain 2 (MLC2), peroxisomal enoyl-CoA hydratase 1 (ECH1), prosomal protein P30-33K (PSMA1) and mutant β-actin by ESI-Q-TOF MS/MS. Also, proton (1H) nuclear magnetic resonance spectroscopy (NMR) was used to elucidate the difference between metabolites in the control and hMSCs treated with H2O2. Among these metabolites, choline and leucine were identified by 1H-NMR as up-regulated metabolites and glycine and proline were identified as down-regulated metabolites.

Original languageEnglish
Pages (from-to)500-510
Number of pages11
JournalExperimental Gerontology
Volume46
Issue number6
DOIs
Publication statusPublished - 2011 Jun

Keywords

  • Cellular senescence
  • Mesenchymal stem cells
  • Metabolomics
  • Proteomics
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

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