title: Altered redox state and apoptosis in the pathogenesis of systemic lupus erythematosus.
abstract: An altered redox status and increased lymphocyte apoptosis have been implicated in the development of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between glutathione (GSH) depletion, reactive oxygen species (ROS) and, the progression of apoptosis and their association with SLE severity. Significant low levels of intracellular glutathione, total thiol and altered redox state (GSH/GSSG) were found in SLE patients, in which lymphocyte apoptosis and activated caspase-3 expression in the lymphocytes were remarkably increased. The severity of disease was positively allied with the increased levels of lymphocyte apoptosis and caspase-3, but negatively with the decreased levels of total thiol, depleted intracellular glutathione and altered redox state (GSH/GSSG). The lymphocyte apoptosis and activated caspase-3 expression were negatively associated with intracellular levels of GSH and redox state and positively associated with the elevated levels of multiple oxidative stress markers; ROS and lipid peroxidation measured as malondialdehyde (MDA). These results suggest that GSH depletion and elevated oxidative stress trigger apoptosis and may be coupled with the severity of the disease.
authors.affiliation: Department of Dermatology, Massachusetts General Hospital (MGH), Harvard Medical School (HMS), Boston, MA, USA.
authors.forename: Dilip
authors.initials: D
authors.lastname: Shah
authors.forename: Sangita
authors.initials: S
authors.lastname: Sah
authors.forename: Ajay
authors.initials: A
authors.lastname: Wanchu
authors.forename: Mei X
authors.initials: MX
authors.lastname: Wu
authors.forename: Archana
authors.initials: A
authors.lastname: Bhatnagar
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000276:immunology; D053148:Caspase 3 / Q000276:immunology / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000097:blood / Q000276:immunology*; D006801:Humans; D015227:Lipid Peroxidation / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000276:immunology; D018384:Oxidative Stress / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000097:blood / Q000276:immunology*; D012720:Severity of Illness Index
chemical_list: D017382:Reactive Oxygen Species; D008315:Malondialdehyde; C505407:CASP3 protein, human; D053148:Caspase 3; D005978:Glutathione