Participation of 47C>T SNP (Ala-9Val polymorphism) of the SOD2 gene in the intracellular environment of human peripheral blood mononuclear cells with and without lipopolysaccharides

• Published in: Molecular and cellular biochemistry 2013, Vol.372 (1-2), p.127-135
• Main Authors: Paludo, Francis Jackson O., Simões-Pires, André, Alho, Clarice S., Gelain, Daniel Pens, Moreira, José Cláudio F.
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Substitution; Antioxidants; Biochemistry; Biomedical and Life Sciences; Blood; Cardiology; Catalase; Cells; Cells, Cultured; Enzymatic activity; Enzymes; Female; Free Radicals - metabolism; Gene polymorphism; Genes; Genetic factors; Genotypes; Glutathione peroxidase; Glutathione Peroxidase - metabolism; Heterozygote; Humans; Inflammation; Intracellular Fluid - enzymology; Leukocytes, Mononuclear - enzymology; Leukocytes, Mononuclear - immunology; Life Sciences; Lipid Peroxidation; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Male; Medical Biochemistry; Nitrites - metabolism; Oncology; Oxidative Stress; Oxidizing agents; Pathogenicity; Pathogens; Peripheral blood mononuclear cells; Peroxidation; Polymorphism; Polymorphism, Single Nucleotide; Sepsis; Single-nucleotide polymorphism; Superoxide dismutase; Superoxide Dismutase - genetics; Tumor Necrosis Factor-alpha - metabolism; Young Adult
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-012-1453-1

The outcome of sepsis occurs due to influence of environmental and genetic factors besides genes variants whose expression support its outcome or not. Oxidative stress is associated to the pathogenicity of sepsis, occurring when there is a reactive species overproduction associated with inflammation. The aim of this study was to characterize the cellular redox status of human peripheral blood mononuclear cells (PBMCs) with either −9Ala (AA) or −9Val (VV) SOD2 genotypes and evaluate their response to oxidative stress induced by lipopolysaccharide (LPS). The PBMCs were isolated from the blood of 30 healthy human volunteers (15 volunteers for each allele) and the following assays were performed: antioxidant enzyme activities (superoxide dismutase; catalase; glutathione peroxidase), total radical-trapping antioxidant parameter, non-enzymatic antioxidant capacity (total antioxidant reactivity), and quantification of conjugated dienes (lipid peroxidation). At basal conditions (i.e., not stimulated by LPS), cells from 47C allele carriers showed higher activities of CAT and SOD, as well as higher TAR compared to 47T allele. However, when 47CC cells were challenged with LPS, we observed a higher shift toward a pro-oxidant state compared to 47TT cells. The CAT activity and lipid peroxidation were increased in cells with both alleles, but SOD activity increased significantly only in 47TT cells. These results demonstrate that SOD2 polymorphisms are associated with different cellular redox environments at both basal and LPS-stimulated states, and identification of this polymorphism may be important for a better understanding of pro-inflammatory conditions.