In Vitro Aging of Human Skin Fibroblasts: Age-Dependent Changes in 4-Hydroxynonenal Metabolism

DOI HANDLE Web Site PubMed 被引用文献1件 参考文献61件
  • Igor Petkovic
    Department of Biosciences, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria
  • Nikolaus Bresgen
    Department of Biosciences, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria
  • Ettore Gilardoni
    Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy
  • Luca Regazzoni
    Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy
  • Koji Uchida
    Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan
  • Giancarlo Aldini
    Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Italy
  • Werner Siems
    Clinics for Prevention and Rehabilitation, Burgstrasse 35, 38667 Bad Harzburg, Germany
  • Peter Eckl
    Department of Biosciences, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria

説明

<jats:p>Evidence suggests that the increased production of free radicals and reactive oxygen species lead to cellular aging. One of the consequences is lipid peroxidation generating reactive aldehydic products, such as 4-hydroxynonenal (HNE) that modify proteins and form adducts with DNA bases. To prevent damage by HNE, it is metabolized. The primary metabolic products are the glutathione conjugate (GSH-HNE), the corresponding 4-hydroxynonenoic acid (HNA), and the alcohol 1,4-dihydroxynonene (DHN). Since HNE metabolism can potentially change during in vitro aging, cell cultures of primary human dermal fibroblasts from several donors were cultured until senescence. After different time points up to 30 min of incubation with 5 µM HNE, the extracellular medium was analyzed for metabolites via liquid chromatography coupled with electrospray ionization mass spectrometry (LC/ESI-MS). The metabolites appeared in the extracellular medium 5 min after incubation followed by a time-dependent increase. But, the formation of GSH-HNL and GSH-DHN decreased with increasing in vitro age. As a consequence, the HNE levels in the cells increase and there is more protein modification observed. Furthermore, after 3 h of incubation with 5 µM HNE, younger cells showed less proliferative capacity, while in older cells slight increase in the mitotic index was noticed.</jats:p>

収録刊行物

被引用文献 (1)*注記

もっと見る

参考文献 (61)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ