Elsakka Noha E, Webster Nigel R, Galley Helen F
Academic Unit of Anaesthesia and Intensive Care, School of Medicine, University of Aberdeen, Aberdeen, UK.
Free Radic Res. 2007 Jul;41(7):770-8. doi: 10.1080/10715760701338828.
Oxidative stress and mitochondrial damage occur in sepsis. Manganese superoxide dismutase (MnSOD) provides the main defence against oxidative stress within mitochondria. Ala9Val is a single nucleotide polymorphism (SNP) in the MnSOD gene, predicted to affect intra-mitochondrial transport of the enzyme. We found a significant difference in the genotype frequency between healthy subjects (n = 100) and patients with sepsis (n = 40, p = 0.009). For assessment of functionality ten healthy subjects of each homozygous genotype (A/A or V/V) were studied. Peripheral blood mononuclear cells were separated and incubated for 18 h with lipopolysaccharide (LPS), followed by analysis of mitochondrial and cytosolic fractions. There was no difference between genotypes in MnSOD activity and cytochrome c concentration, and minor differences in total antioxidant capacity (TAC) and mitochondrial membrane potential, which did not affect response to LPS. Despite predictions from structural enzyme studies that mitochondrial trafficking would be affected by the Ala9Val polymorphism of the MnSOD gene had little functional effect.
脓毒症中会发生氧化应激和线粒体损伤。锰超氧化物歧化酶（MnSOD）是线粒体抵御氧化应激的主要防线。Ala9Val是MnSOD基因中的一个单核苷酸多态性（SNP），预计会影响该酶在线粒体内的转运。我们发现健康受试者（n = 100）和脓毒症患者（n = 40，p = 0.009）之间的基因型频率存在显著差异。为了评估功能，对每种纯合基因型（A/A或V/V）的10名健康受试者进行了研究。分离外周血单个核细胞，并用脂多糖（LPS）孵育18小时，然后分析线粒体和胞质组分。基因型之间的MnSOD活性和细胞色素c浓度没有差异，总抗氧化能力（TAC）和线粒体膜电位存在微小差异，但不影响对LPS的反应。尽管结构酶研究预测MnSOD基因的Ala9Val多态性会影响线粒体运输，但实际上其功能影响很小。
