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
Journal
Clinical and Developmental Immunology
Journal Volume
2012
Date Issued
2012
Author(s)
Abstract
Urinary excretion of N-benzoyl-glycyl-N-(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 -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. Copyright ? 2012 Ko-Jen Li et al.
SDGs
Other Subjects
8 hydroxydeoxyguanosine; adenosine triphosphate; amino acid derivative; azathioprine; CD53 antigen; creatinine; gamma glutamyltransferase; glucose transporter; glucose transporter 3; glucose transporter 6; glutathione; glutathione peroxidase; hydroxychloroquine; lactic acid; n benzoylglycyl n epsilon(hexanoyl)lysine; prednisolone; unclassified drug; biological marker; drug derivative; gamma glutamyltransferase; glucose transporter; glucose transporter 3; glutathione peroxidase; lysine; SLC2A9 protein, human; adult; article; bioenergy; controlled study; disease activity; disease duration; enzyme activity; fatty acid oxidation; female; glucose transport; human; human cell; major clinical study; male; neutrophil; oxidation reduction state; oxidative stress; priority journal; protein expression; systemic lupus erythematosus; T lymphocyte; urinary excretion; adolescent; brain vasculitis; energy metabolism; gene expression regulation; genetics; immunology; metabolism; oxidation reduction reaction; oxidative stress; pathology; pathophysiology; urine; Adolescent; Adult; Biological Markers; Energy Metabolism; Female; gamma-Glutamyltransferase; Gene Expression Regulation, Enzymologic; Glucose Transport Proteins, Facilitative; Glucose Transporter Type 3; Glutathione Peroxidase; Humans; Lupus Vasculitis, Central Nervous System; Lysine; Male; Neutrophils; Oxidation-Reduction; Oxidative Stress; T-Lymphocytes
Type
journal article