Capeleto Dianni, Barbisan Fernanda, Azzolin Verônica, Dornelles Eduardo Bortoluzzi, Rogalski Felipe, Teixeira Cibele Ferreira, Machado Alencar Kolinski, Cadoná Francine Carla, da Silva Tális, Duarte Thiago, Duarte Marta Maria Medeiros Frescura, da Cruz Ivana Beatrice Mânica
Pharmacology Graduate Program, Federal University of Santa Maria (UFSM), Av. Roraima 1000, Prédio 19, Santa Maria, RS, 90105900, Brazil.
Biogerontology. 2015 Oct;16(5):621-30. doi: 10.1007/s10522-015-9561-4. Epub 2015 Mar 10.
Resveratrol is an molecule that provides both anti-inflammatory and antioxidant properties. However, it is unclear whether the basal oxidative state of the cell has any influence on the effects of this compound. In humans, a single nucleotide polymorphism (SNP) is present in the enzyme manganese superoxide dismutase (SOD2), localized in codon 16 (rs4880), which can either be an alanine (A) or valine (V). This SNP causes an imbalance in the cellular levels of SOD2, where AA- and VV-genotypes result in higher or lower enzymatic activity, respectively. Furthermore, the VV-genotype has been associated with high levels of inflammatory cytokines. Here, we examined the effects of a range of resveratrol concentrations on the in vitro activation of human peripheral blood mononuclear cells (PBMCs) carrying different Ala16Val-SOD2 genotypes. Cell proliferation, several oxidative biomarkers and cytokines (IL-1β, IL-6, TNFα, Igγ and IL-10) were analyzed. In addition, the effects of resveratrol on the expression of the sirt1 gene were evaluated by qRT-PCR. After 24 h exposure to resveratrol, A-genotype PBMCs displayed a decrease in cell proliferation, whilst VV-cells contrasted; At 10 µM resveratrol, there was a significant decrease in the production of inflammatory cytokines in A-allele cells; however, VV-cells generally displayed a subtle decrease in these, except for TNFα, which was not affected. In all SOD2 genotypes cells exposed to resveratrol resulted in an upregulation of Sirt1 levels. Together, these results suggest that the effect of resveratrol on human PBMC activation is not universal and is dependent on the Ala16Val-SOD2 SNP.
白藜芦醇是一种具有抗炎和抗氧化特性的分子。然而，尚不清楚细胞的基础氧化状态是否会对该化合物的作用产生任何影响。在人类中，位于密码子16（rs4880）的锰超氧化物歧化酶（SOD2）中存在一种单核苷酸多态性（SNP），它可以是丙氨酸（A）或缬氨酸（V）。这种SNP会导致SOD2细胞水平失衡，其中AA基因型和VV基因型分别导致较高或较低的酶活性。此外，VV基因型与高水平的炎性细胞因子有关。在此，我们研究了一系列白藜芦醇浓度对携带不同Ala16Val-SOD2基因型的人外周血单个核细胞（PBMC）体外活化的影响。分析了细胞增殖、几种氧化生物标志物和细胞因子（IL-1β、IL-6、TNFα、Igγ和IL-10）。此外，通过qRT-PCR评估白藜芦醇对sirt1基因表达的影响。在暴露于白藜芦醇24小时后，A基因型PBMC的细胞增殖减少，而VV细胞则相反；在10μM白藜芦醇时，A等位基因细胞中炎性细胞因子的产生显著减少；然而，VV细胞通常在这些方面表现出轻微下降，但TNFα不受影响。在所有暴露于白藜芦醇的SOD2基因型细胞中，Sirt1水平均上调。总之，这些结果表明白藜芦醇对人PBMC活化的作用并非普遍存在，而是依赖于Ala16Val-SOD2 SNP。
