title: The antioxidant effect exerted by TGF-1beta-stimulated hyaluronan production reduced NF-kB activation and apoptosis in human fibroblasts exposed to FeSo4 plus ascorbate.
abstract: Previous studies suggest that Transforming growth factor-1beta (TGF-1beta) administration in human fibroblasts exposed to oxidative stress is able to modulate hyaluronan synthases (HASs). HAS modulation in turn increases high molecular weight (Hyaluronan) HA concentration. Nuclear factor kB (NF-kB) is a response transcription factor involved in inflammation and acts by enabling the expression of certain detrimental molecules. Caspases are specific proteases responsible for regulating and programming cell death. HA at medium molecular weight together with chondroitin-4-sulphate proved to be effective on NF-kB and caspases. We investigated whether the protective effect afforded by the high molecular weight HA produced by TGF-1beta treatment has any effect on NF-kB and apoptosis activation in fibroblast cultures exposed to oxidative stress. Generation of free radicals gives rise to cell death, increases lipid peroxidation, activates NF-kB, reduces its cytoplasmic inhibitor IkBalpha, augments caspase-3 and caspase-7 gene expression and their relative protein activity, and depletes catalase (CAT) and glutathione peroxidase (GPx). Treatment of fibroblasts with TGF-1beta 12 h before inducing oxidative stress greatly increased HA levels, ameliorated cell survival, inhibited lipid peroxidation, blunted NF-kB translocation, normalized IkBalpha protein, reduced caspase gene expression and protein levels, and restored the endogenous antioxidants CAT and GPx. Since it was previously reported that antioxidants can work as inhibitors of NF-kB and apoptosis induction we can hypothesize that endogenous HA, by inhibiting lipid peroxidation, may block a step whereby free radical activity converges in the signal transduction pathway leading to NF-kB and caspase activation.
authors.affiliation: Department of Biochemical, Physiological and Nutritional Sciences, School of Medicine, University of Messina, Policlinico Universitario, Torre Biologica, 5 degree piano, Via C. Valeria, 98125 Messina, Italy. gcampo@unime.it
authors.forename: Giuseppe M
authors.initials: GM
authors.lastname: Campo
authors.forename: Angela
authors.initials: A
authors.lastname: Avenoso
authors.forename: Salvatore
authors.initials: S
authors.lastname: Campo
authors.forename: Angela
authors.initials: A
authors.lastname: D'Ascola
authors.forename: Paola
authors.initials: P
authors.lastname: Traina
authors.forename: Dario
authors.initials: D
authors.lastname: Samà
authors.forename: Alberto
authors.initials: A
authors.lastname: Calatroni
mesh_terms: D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D058085:Iron Compounds / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D058085:Iron Compounds; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D006820:Hyaluronic Acid; D053148:Caspase 3; D053179:Caspase 7; D001205:Ascorbic Acid