Oxidative stress contributes to accelerated development of the senescent phenotype in human peritoneal mesothelial cells exposed to high glucose

Krzysztof Ksiazek, Andrzej Breborowicz, Achim Jörres, Janusz Witowski

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Increasing evidence indicates that cells exposed to high glucose exhibit shortened proliferative lifespan and enter the state of senescence earlier. However, the contribution of hyperglycemia-induced oxidative stress to premature cell senescence is not entirely clear. In the current study we have examined the role of oxidative stress in cellular senescence of human peritoneal mesothelial cells (HPMC) exposed to high glucose. The experiments were performed on primary omental-derived HPMC grown into senescence in the presence of normal (5 mM) and high (30 mM) glucose. Senescence of HPMC was associated with increased generation of reactive oxygen species (ROS) and decreased cellular glutathione (GSH). Exposure to high glucose significantly exacerbated these effects and increased the level of senescence-associated β-galactosidase (SA-β-Gal) and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) expression. Furthermore, high glucose markedly increased senescence-related HPMC hypertrophy. The addition of L-2-oxothiazolidine-4-carboxylic acid, a GSH precursor, restored partially GSH levels and decreased ROS release. This effect was associated with reduced levels of SA-β-Gal and 8-OH-dG, diminished TGF-β1 and fibronectin release, and less pronounced hypertrophy of aged HPMC. These results indicate that the accelerated senescence response in HPMC exposed to high glucose is strongly related to oxidative stress.

Original languageEnglish (US)
Pages (from-to)636-641
Number of pages6
JournalFree Radical Biology and Medicine
Volume42
Issue number5
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Fingerprint

Oxidative stress
Oxidative Stress
Phenotype
Glucose
Galactosidases
Cell Aging
Reactive Oxygen Species
Hypertrophy
Fibronectins
Glutathione
Hyperglycemia
8-oxo-7-hydrodeoxyguanosine
Experiments

Keywords

  • Free Radicals
  • Glucose
  • Mesothelial cells
  • Oxidative stress
  • Senescence

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Oxidative stress contributes to accelerated development of the senescent phenotype in human peritoneal mesothelial cells exposed to high glucose. / Ksiazek, Krzysztof; Breborowicz, Andrzej; Jörres, Achim; Witowski, Janusz.

In: Free Radical Biology and Medicine, Vol. 42, No. 5, 01.03.2007, p. 636-641.

Research output: Contribution to journalArticle

Ksiazek, Krzysztof ; Breborowicz, Andrzej ; Jörres, Achim ; Witowski, Janusz. / Oxidative stress contributes to accelerated development of the senescent phenotype in human peritoneal mesothelial cells exposed to high glucose. In: Free Radical Biology and Medicine. 2007 ; Vol. 42, No. 5. pp. 636-641.
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