title: Role of altered mitochondria functions in the pathogenesis of systemic lupus erythematosus.
abstract: Mitochondria, main producers of reactive-oxygen species (ROS), were studied to examine their role in the pathogenesis of systemic lupus erythematosus (SLE). PBMCs and mitochondria were isolated from SLE patients and healthy volunteers for various parameters. Mitochondrial ROS, swelling, hyperpolarization and levels of cytochrome c, caspase3 in the cells were assessed by flow cytometry. ROS was significantly increased in SLE patients (SLE vs controls: 1.83 ± 1.03 vs 1.10 ± 0.35; p < 0.0001). Depolarized state of mitochondria was greater in patients (SLE vs controls: 7.10 ± 5.50% vs 2.5 ± 1.8%; p < 0.05). Mitochondria swelling was found to be significantly altered in patients (SLE vs controls: 112.65 ± 36.56 vs 60.49 ± 20.69; p < 0.001). Expression of cytochrome c and caspase 3 (SLE vs controls: 1.37 ± 0.37% vs 1.01 ± 0.03%; 1.57 ± 0.46% vs 1.06 ± 0.07%; p < 0.05) respectively was found to be significantly increased in SLE. Further, the enzymatic activity of mitochondrial complex was assessed in isolated mitochondria. A significant decrease in activity of Complex I (SLE vs controls: 11.79 ± 3.18 vs 15.10 ± 6.38 nmol NADH oxidized/min/mg protein, p < 0.05); Complex IV (SLE vs control: 9.41 ± 5.16 vs 13.56 ± 5.92 nmol cytochrome c oxidized/min/mg protein, p < 0.05) and Complex V (SLE vs controls: 4.85 ± 1.39 vs 6.17 ± 2.02 nmol ATP hydrolyzed/min/mg protein, p < 0.05) was found in SLE patients in comparison to healthy controls. However, Complex II did not show significant variation in either group (SLE vs controls: 42.2 ± 28.6 vs 61.71 ± 42.3 nmol succinate oxidized/min/mg protein; ns). The decrease in enzyme activities of mitochondrial Complexes I, IV and V on one hand and ROS, hyperpolarization and apoptosis on the other points toward a possible role of mitochondria in the pathogenesis of lupus.
authors.affiliation: Department of Biochemistry, Basic Medical Sciences Block, Panjab University, Chandigarh, India.
authors.forename: B D
authors.initials: BD
authors.lastname: Leishangthem
authors.affiliation: Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, Basic Medical Sciences Block, Panjab University, Chandigarh, India bhatnagar.archana@gmail.com bhatnagar@pu.ac.in.
authors.forename: A
authors.initials: A
authors.lastname: Bhatnagar
mesh_terms: D000328:Adult; D017209:Apoptosis; D016022:Case-Control Studies; D053148:Caspase 3 / Q000032:analysis; D045304:Cytochromes c / Q000032:analysis; D045222:Electron Transport Chain Complex Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000201:enzymology* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D008933:Mitochondrial Swelling; D017382:Reactive Oxygen Species / Q000032:analysis
chemical_list: D045222:Electron Transport Chain Complex Proteins; D017382:Reactive Oxygen Species; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Apoptosis; mitochondria complexes; mitochondria dysfunction