41 research outputs found
Human SOD2 Modification by Dopamine Quinones Affects Enzymatic Activity by Promoting Its Aggregation: Possible Implications for Parkinsonâs Disease
Mitochondrial dysfunction and oxidative stress are considered central in dopaminergic neurodegeneration in Parkinsonâs disease (PD). Oxidative stress occurs when the endogenous antioxidant systems are overcome by the generation of reactive oxygen species (ROS). A plausible source of oxidative stress, which could account for the selective degeneration of dopaminergic neurons, is the redox chemistry of dopamine (DA) and leads to the formation of ROS and reactive dopamine-quinones (DAQs). Superoxide dismutase 2 (SOD2) is a mitochondrial enzyme that converts superoxide radicals to molecular oxygen and hydrogen peroxide, providing a first line of defense against ROS. We investigated the possible interplay between DA and SOD2 in the pathogenesis of PD using enzymatic essays, site-specific mutagenesis, and optical and high-field-cw-EPR spectroscopies. Using radioactive DA, we demonstrated that SOD2 is a target of DAQs. Exposure to micromolar DAQ concentrations induces a loss of up to 50% of SOD2 enzymatic activity in a dose-dependent manner, which is correlated to the concomitant formation of protein aggregates, while the coordination geometry of the active site appears unaffected by DAQ modifications. Our findings support a model in which DAQ-mediated SOD2 inactivation increases mitochondrial ROS production, suggesting a link between oxidative stress and mitochondrial dysfunction
High systemic IL-6 is associated with worse prognosis in patients with non-small cell lung cancer
Characteristic cytokine patterns have been described in different cancer patients and they are related to their diagnosis, prognosis, prediction of treatment responses and survival. A panel of cytokines was evaluated in the plasma of non-small cell lung cancer (NSCLC) patients and healthy controls to investigate their profile and relationship with clinical characteristics and overall survival. The case-controlled cross-sectional study design recruited 77 patients with confirmed diagnosis of NSCLC (cases) and 91 healthy subjects (controls) aimed to examine peripheral pro-inflammatory and anti-inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF and IFN-gamma) by Cytometry Beads Arrays (CBA Flex) in. The cytokine IL-6 showed a statistically significant difference among groups with increased expression in the case group (p < 0.001). The correlation between the cytokines expression with patient's clinical characteristics variables revealed the cytokine IL-6 was found to be associated with gender, showing higher levels in male (p = 0.036), whereas IL-17A levels were associated with TNM stage, being higher in III-IV stages (p = 0.044). We observed worse overall survival for individuals with high levels of IL-6 when compared to those with low levels of this cytokine in 6, 12 and 24 months. Further studies of IL-6 levels in independent cohort could clarify the real role of IL-6 as an independent marker of prognostic of NSCLC.Conselho Nacional de Desenvolvimento CientĂfico e TencnolĂłgico (CNPq) [Grant number 401775/2012-7 to ALF]; Fundação de Amparo Ă Pesquisa do Estado de SĂŁo Paulo (FAPESP) [Grant number 2014/ 23414-8 to EMS]info:eu-repo/semantics/publishedVersio
International Consensus Statement on Rhinology and Allergy: Rhinosinusitis
Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICARâRS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICARâRSâ2021 as well as updates to the original 140 topics. This executive summary consolidates the evidenceâbased findings of the document. Methods: ICARâRS presents over 180 topics in the forms of evidenceâbased reviews with recommendations (EBRRs), evidenceâbased reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICARâRSâ2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidenceâbased management algorithm is provided. Conclusion: This ICARâRSâ2021 executive summary provides a compilation of the evidenceâbased recommendations for medical and surgical treatment of the most common forms of RS
Copper depletion/repletion of human ceruloplasmin is followed by the changes in its spectral features and functional properties
Copper ions of different types were gradually eliminated
from ceruloplasmin (CPI; ferro-O2-oxidoreductase, EC
1.16.3.1.) by dialyzing the enzyme against KCN. Protein
was sampled 2, 4, 6, 22, and 28 b after the dialysis
started. Atomic absorption allowed us to estimate the
amount of copper atoms per CP molecule. Light absorption
in the UV and visible regions along with fluorescence
and EPR spectra were also registered. Oxidase and
dismutase activitites of the enzyme were measured at
each step. The combination of the data tbns obtained
allowed us to trace the sequence of CP depletion of certain
copper ions. The same methods were applied in reconstitution
studies to detect the return of different types of Cu 2 +. The experiments were performed on CP samples differing in the amount of copper still bound after CN - treatment. It is shown that the oxidase activity is efficiently brought back to CP if, after the dialysis against cyanide, the catalytic center had preserved its type 3 Cu2+. Dismutase activity of CP did not depend greatly
on the presence or absence of type 1 and type 2 copper ions. The results obtained allow a more precise evaluation of the role of different types Cu 2 + in the assembly of the complex catalytic center of CP and in the accomplishment by the enzyme of its multiple functions