title: Deranged bioenergetics and defective redox capacity in T lymphocytes and neutrophils are related to cellular dysfunction and increased oxidative stress in patients with active systemic lupus erythematosus.
abstract: Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyl)lysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE) than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox) capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T) and polymorphonuclear neutrophils (PMN) of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px) and γ-glutamyl-transpeptidase (GGT), was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients.
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei 100, Taiwan.
authors: Ko-Jen
authors: KJ
authors: Li
authors: Cheng-Han
authors: CH
authors: Wu
authors: Song-Chou
authors: SC
authors: Hsieh
authors: Ming-Chi
authors: MC
authors: Lu
authors: Chang-Youh
authors: CY
authors: Tsai
authors: Chia-Li
authors: CL
authors: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000652:urine; D004734:Energy Metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020945:Lupus Vasculitis, Central Nervous System / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008239:Lysine / Q000031:analogs & derivatives / Q000652:urine; D008297:Male; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005723:gamma-Glutamyltransferase / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051246:Glucose Transport Proteins, Facilitative; D051274:Glucose Transporter Type 3; C411811:SLC2A9 protein, human; D005979:Glutathione Peroxidase; D005723:gamma-Glutamyltransferase; D008239:Lysine