The subunit composition of human extracellular superoxide dismutase (EC-SOD) regulate enzymatic activity-1

<p><b>Copyright information:</b></p><p>Taken from "The subunit composition of human extracellular superoxide dismutase (EC-SOD) regulate enzymatic activity"</p><p>http://www.biomedcentral.com/1471-2091/8/19</p><p>BMC Biochemistry 2007;8():19-19.</p><p>Published online 15 Oct 2007</p><p>PMCID:PMC2100054.</p><p></p> inactive (iEC-SOD; gray circles). Our results show that the two different subunits can combine to form dimers with variable activities. Tetrameric EC-SOD is maintained by interactions within the N-terminal region, which are likely to be unaffected by the folding of the catalytic domain. We thus propose that dimers combine to generate five different tetramers with distinct SOD activities. The relative SOD activity of each structural level is indicated below each structure. The presence or absence of the ECM-binding regions is not indicated, as this is likely not affecting the tetramer assembly

The subunit composition of human extracellular superoxide dismutase (EC-SOD) regulate enzymatic activity-4

<p><b>Copyright information:</b></p><p>Taken from "The subunit composition of human extracellular superoxide dismutase (EC-SOD) regulate enzymatic activity"</p><p>http://www.biomedcentral.com/1471-2091/8/19</p><p>BMC Biochemistry 2007;8():19-19.</p><p>Published online 15 Oct 2007</p><p>PMCID:PMC2100054.</p><p></p>e F) separates into the disulfide-linked dimer and monomers. The monomers are resolved into aEC-SOD and iEC-SOD as previously shown [23]. The dimer migrates as a fuzzy band of ~52 kDa. When EC-SOD is deglycosylated (+PNGase F) the size of the monomers and dimer is reduced consistent with the removal of a single glycan in each subunit. The deglycosylated dimer resolved into three closely migrating bands of 45 – 49 kDa denoted α, β, and γ as indicated. The position of the deglycosylated monomers is indicated. The gel was stained by Coomassie brilliant blue. A molecular weight marker is indicated on the left. Deglycosylation of EC-SOD improved the separation in non-reduced SDS-PAGE and revealed that the disulfide-bonded dimer migrates as 3 bands most likely caused by differences in folding

The subunit composition of human extracellular superoxide dismutase (EC-SOD) regulate enzymatic activity-3

<p><b>Copyright information:</b></p><p>Taken from "The subunit composition of human extracellular superoxide dismutase (EC-SOD) regulate enzymatic activity"</p><p>http://www.biomedcentral.com/1471-2091/8/19</p><p>BMC Biochemistry 2007;8():19-19.</p><p>Published online 15 Oct 2007</p><p>PMCID:PMC2100054.</p><p></p>ted by reverse-phase HPLC. Two peaks indicate the presence of aEC-SOD (35.5 min) or iEC-SOD (38.2 min) as indicated. Three data sets were collected: F1, solid line; F2, dashed line; F3, dotted line) and normalized using the peak representing Val24-Arg34 (*). The yield of this peptide did not differ between aEC-SOD and iEC-SOD. The level of the two folding variants could be estimated by measuring the ratio of absorbance between the peaks representing aEC-SOD and iEC-SOD and the Val24-Arg34 peptide. The obtained ratio is indicated

The subunit composition of human extracellular superoxide dismutase (EC-SOD) regulate enzymatic activity-0

<p><b>Copyright information:</b></p><p>Taken from "The subunit composition of human extracellular superoxide dismutase (EC-SOD) regulate enzymatic activity"</p><p>http://www.biomedcentral.com/1471-2091/8/19</p><p>BMC Biochemistry 2007;8():19-19.</p><p>Published online 15 Oct 2007</p><p>PMCID:PMC2100054.</p><p></p> inactive (iEC-SOD; gray circles). Our results show that the two different subunits can combine to form dimers with variable activities. Tetrameric EC-SOD is maintained by interactions within the N-terminal region, which are likely to be unaffected by the folding of the catalytic domain. We thus propose that dimers combine to generate five different tetramers with distinct SOD activities. The relative SOD activity of each structural level is indicated below each structure. The presence or absence of the ECM-binding regions is not indicated, as this is likely not affecting the tetramer assembly

The subunit composition of human extracellular superoxide dismutase (EC-SOD) regulate enzymatic activity-2

<p><b>Copyright information:</b></p><p>Taken from "The subunit composition of human extracellular superoxide dismutase (EC-SOD) regulate enzymatic activity"</p><p>http://www.biomedcentral.com/1471-2091/8/19</p><p>BMC Biochemistry 2007;8():19-19.</p><p>Published online 15 Oct 2007</p><p>PMCID:PMC2100054.</p><p></p>ide bonding indicated and tryptic cleavage sites generating cysteine-containing peptides shown by arrows. Following cleavage by trypsin, aEC-SOD is represented by a disulfide-linked triple peptide and iEC-SOD represented by a disulfide-linked double peptide. These two structures can be separated by RP-HPLC and can thus be used to detect the presence of the two folding variants

The impact of genetic variation and cigarette smoke on DNA methylation in current and former smokers from the COPDGene study

<p>DNA methylation can be affected by systemic exposures, such as cigarette smoking and genetic sequence variation; however, the relative impact of each on the epigenome is unknown. We aimed to assess if cigarette smoking and genetic variation are associated with overlapping or distinct sets of DNA methylation marks and pathways. We selected 85 Caucasian current and former smokers with genome-wide single nucleotide polymorphism (SNP) genotyping available from the COPDGene study.  Genome-wide methylation was obtained on DNA from whole blood using the Illumina HumanMethylation27 platform. To determine the impact of local sequence variation on DNA methylation (mQTL), we examined the association between methylation and SNPs within 50 kb of each CpG site.  To examine the impact of cigarette smoking on DNA methylation, we examined the differences in methylation by current cigarette smoking status. We detected 770 CpG sites annotated to 708 genes associated at an FDR < 0.05 in the cis-mQTL analysis and 1,287 CpG sites annotated to 1,242 genes, which were nominally associated in the smoking-CpG association analysis (<i>P</i>_unadjusted < 0.05). Forty-three CpG sites annotated to 40 genes were associated with both SNP variation and current smoking; this overlap was not greater than that expected by chance. Our results suggest that cigarette smoking and genetic variants impact distinct sets of DNA methylation marks, the further elucidation of which may partially explain the variable susceptibility to the health effects of cigarette smoking. Ascertaining how genetic variation and systemic exposures differentially impact the human epigenome has relevance for both biomarker identification and therapeutic target development for smoking-related diseases.</p

Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts

Background: Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes.Methods: We constructed a polygenic risk score using a genome wide association study of lung function (FEV1 and FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC Findings: The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74–1·88] and non-European (1·42 [1·34–1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56–9·72) in European ancestry and 4·83 (3·45–6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79–0·81] vs 0·76 [0·75 0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern. Interpretation: A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtypes associated with cigarette smoking, and patterns of reduced lung growth.</div