title: Oxidative stress contributes to accelerated development of the senescent phenotype in human peritoneal mesothelial cells exposed to high glucose.
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 beta-galactosidase (SA-beta-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-beta-Gal and 8-OH-dG, diminished TGF-beta1 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.
authors.affiliation: Department of Pathophysiology, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Ksiazek
authors.forename: Andrzej
authors.initials: A
authors.lastname: Breborowicz
authors.forename: Achim
authors.initials: A
authors.lastname: Jörres
authors.forename: Janusz
authors.initials: J
authors.lastname: Witowski
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005981:Glutathione Synthase / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D010529:Peritoneal Cavity / Q000166:cytology; D010641:Phenotype; D011761:Pyrrolidonecarboxylic Acid / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology; D000094765:Glutathione Peroxidase GPX1
chemical_list: D017382:Reactive Oxygen Species; D053778:Thiazolidines; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005979:Glutathione Peroxidase; D005981:Glutathione Synthase; D003849:Deoxyguanosine; D005947:Glucose; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human