Modulation of telomerase gene expression of activated peripheral blood mononuclear cells is influenced by Ala16Val-Sod2 gene polymorphism
Fernanda Barbisan, Dianni Capelleto, Veronica Azzolin, Eduardo Bortoluzzi Dornelles, Francine Carla Cadona, Alencar Kolinski Machado, Cybele Ferreira Teixeira,Glauber Wagner, Euler Esteves Ribeiro, Ivana Beatrice Mânica da Cruz
Universidade Federal de Santa Maria, Av Roraima 1000, Santa Maria-RS, 97105-900, RS Brazil Universidade do Oeste de Santa Catarina,
: J Regen Med
Abstract
The activation process of T and B-lymphocytes involves the increase in cellular proliferation and upregulation of telomerase activity, comparable to those observed in stem cells and transformed cell lines. However, aging decline of total number of T and B-lymphocytes(immunosenescence) due decrease in the telomerase activity that is responsible to telomeric DNA region restoration. As immunosenescence is a process that present individuals variation, the influence of genetic alteration of oxidative stress metabolism on telomerase gene expression of activated lymphocytes, need to be elucidated. Human beings present a superoxide dismutase manganese dependent (SOD2 ) single nucleotide polymorphism (SNP) (rs4880 in 16 codon (Ala16Val-SOD2 ) generating three genotypes. Both homozygous genotypes create imbalance in O-2– H2 O2 levels due change in SOD2 efficiency (VV = low efficiency; AA= high efficiency) and has been associated with chronic diseases and differential response to drug and toxicants exposition.Therefore, we evaluated the effect of SOD2-SNP cell expansion, viability and telomerase expression of peripheral blood mononuclear cells (PBMCs) from subjects with different Ala16Val-SOD2 genotypes (n=12). PBMCs were cultured in RPMI 1340 in controlled conditions (CO2 5%-37oC) and the viability/cells proliferation was evaluated by MTT assay and flow cytometry (cell cycle and apoptosis induction) after 1, 3, 7 and 14 days. The telomerase modulation was analyzed by qRT-PCR and telomere shortening by ELISA immunoassay. Whereas, after 3 three days exposition AA-PBMCs presented high proliferative rate than other genotypes, from this period also occur a fast loss of proliferation and apoptosis processes. After 15 days just VV genotype presented up regulation of telomerase gene.The present study corroborate the hypothesis that proliferation-imunosenescence is broadly regulated by O-2 – H2 O2 mitochondrial levels.
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