title: Antioxidant status in J774A.1 macrophage cell line during chronic exposure to glycated serum.
abstract: Advanced glycation end-products (AGEs) are linked to aging and correlated diseases. The aim of present study was to evaluate oxidative stress related parameters in J774A.1 murine macrophage cells during chronic exposure to a subtoxic concentration of AGE (5% ribose-glycated serum (GS)) and subsequently for 48 h to a higher dose (10% GS). No effects on cell viability were evident in either experimental condition. During chronic treatment, glycative markers (free and bound pentosidine) increased significantly in intra- and extracellular environments, but the production and release of thiobarbituric acid reactive substances (TBARs), as an index of lipid peroxidation, underwent a time-dependent decrease. Exposure to 10% GS evidenced that glycative markers rose further, while TBARs elicited a cellular defence against oxidative stress. Nonadapted cultures showed an accumulation of AGEs, a marked oxidative stress, and a loss of viability. During 10% GS exposure, reduced glutathione levels in adapted cultures remained constant, as did the oxidized glutathione to reduced glutathione ratio, while nonadapted cells showed a markedly increased redox ratio. A constant increase of heat shock protein 70 (HSP70) mRNA was observed in all experimental conditions. On the contrary, HSP70 expression became undetectable for a longer exposure time; this could be due to the direct involvement of HSP70 in the refolding of damaged proteins. Our findings suggest an adaptive response of macrophages to subtoxic doses of AGE, which could constitute an important factor in the spread of damage to other cellular types during aging.
authors.affiliation: Department of Experimental Medicine, Section of General Pathology, University of Genoa, Italy. ambassi@medicina.unige.it
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Bassi
authors.forename: Sabina
authors.initials: S
authors.lastname: Ledda
authors.forename: Maria Clara
authors.initials: MC
authors.lastname: De Pascale
authors.forename: Susanna
authors.initials: S
authors.lastname: Penco
authors.forename: Simona
authors.initials: S
authors.lastname: Rossi
authors.forename: Patrizio
authors.initials: P
authors.lastname: Odetti
authors.forename: Damiano
authors.initials: D
authors.lastname: Cottalasso
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000009:adverse effects*; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004781:Environmental Exposure / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017127:Glycation End Products, Advanced; D018840:HSP70 Heat-Shock Proteins; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D001120:Arginine; C062187:pentosidine; D005978:Glutathione; D008239:Lysine