Exercise training decreases the load and changes the content of circulating SDS-resistant protein aggregates in patients with heart failure with reduced ejection fraction

BackgroundHeart failure (HF) often disrupts the protein quality control (PQC) system leading to protein aggregate accumulation. Evidence from tissue biopsies showed that exercise restores PQC system in HF; however, little is known about its effects on plasma proteostasis.AimTo determine the effects of exercise training on the load and composition of plasma SDS-resistant protein aggregates (SRA) in patients with HF with reduced ejection fraction (HFrEF).MethodsEighteen patients with HFrEF (age: 63.4 +/- 6.5 years; LVEF: 33.4 +/- 11.6%) participated in a 12-week combined (aerobic plus resistance) exercise program (60 min/session, twice per week). The load and content of circulating SRA were assessed using D2D SDS-PAGE and mass spectrometry. Cardiorespiratory fitness, quality of life, and circulating levels of high-sensitive C-reactive protein, N-terminal pro-B-type natriuretic peptide (NT-proBNP), haptoglobin and ficolin-3, were also evaluated at baseline and after the exercise program.ResultsThe exercise program decreased the plasma SRA load (% SRA/total protein: 38.0 +/- 8.9 to 36.1 +/- 9.7%, p = 0.018; % SRA/soluble fraction: 64.3 +/- 27.1 to 59.8 +/- 27.7%, p = 0.003). Plasma SRA of HFrEF patients comprised 31 proteins, with alpha-2-macroglobulin and haptoglobin as the most abundant ones. The exercise training significantly increased haptoglobin plasma levels (1.03 +/- 0.40 to 1.11 +/- 0.46, p = 0.031), while decreasing its abundance in SRA (1.83 +/- 0.54 x 1011 to 1.51 +/- 0.59 x 1011, p = 0.049). Cardiorespiratory fitness [16.4(5.9) to 19.0(5.2) ml/kg/min, p = 0.002], quality of life, and circulating NT-proBNP [720.0(850.0) to 587.0(847.3) pg/mL, p = 0.048] levels, also improved after the exercise program.ConclusionExercise training reduced the plasma SRA load and enhanced PQC, potentially via haptoglobin-mediated action, while improving cardiorespiratory fitness and quality of life of patients with HFrEF.Fundacao para a Ciencia e a Tecnologia (FCT), POCI-01-0145-FEDER-030011, Fundação para a Ciências e a Tecnologia (FCT) BEX 0554/14 - 6info:eu-repo/semantics/publishedVersio

Thirty second annual meeting 1996

209 P.Honduras fue el escenario de la 32 ª reunión anual de los neumáticos del Caribe Cultivos Alimentarios Sociedad. Aunque Honduras es física, cultural e históricamente una parte integral de la Cuenca del Caribe de los neumáticos, esta fue la primera vez que la sociedad convocada en América Central. La historia nos muestra ejemplos de esta integración. Hace siglos los mayas exporta su comercio y la cultura, ya que los juegos de pelota narrados en las mayores islas del Caribe atestiguan. Hace más de 500 años, los españoles y los británicos batallas territoriales luchado a lo largo de la costa de la incrustación de manera permanente las dos alcalde idiomas que se utilizan hoy en día en América Central

Notas de clases 1994

115 P.Este curso ha sido diseñado para guiar al estudiante a visualizar los componentes físicos y biológicos asociados directo y/o indirectamente con la fisiología vegetal. A diferencia de otros métodos de enseñanza de fisiología, este curso pretende llevar al estudiante por un camino donde podrá visualizar y entender el microambiente y al mismo tiempo podrá visualizar y comprender los procesos abstractos a nivel molecular, característicos de la fisiología vegetal

From hexamer to amyloid: marginal stability of apolipoprotein SAA2.2 leads to in vitro fibril formation at physiological temperature

Serum amyloid A (SAA) is a major acute phase reactant and a small apolipoprotein of high density lipoproteins (HDL) in the serum. In cases of prolonged inflammation, SAA may form amyloid fibrils, leading to the disease of amyloid A (AA) amyloidosis. Recently, we have shown that murine SAA2.2, a non-amyloidogenic isoform in vivo, forms a hexamer in vitro containing a putative central channel. It is reported herein that upon thermal denaturation, hexameric SAA2.2 irreversibly dissociates to a misfolded monomer at physiological temperature, formation of which coincides with a significant loss of alpha-helical and gain of beta-sheet structure. When SAA2.2 is incubated for several days at 37 degrees C, sedimentation analytical ultracentrifugation reveals the presence of soluble high molecular weight aggregates, which upon further incubation undergo subsequent self-assembly into amyloid fibrils. Limited proteolysis experiments suggest that the in vitro amyloidogenecity of SAA2.2 is related to structural alteration in its N-terminus. Our observation that SAA2.2 can form amyloid fibrils in vitro at physiological temperatures suggests that SAA2.2's inability to cause amyloidosis may be related to other factors, such as the stabilization of hexameric SAA2.2 (possibly through ligand binding), and/or the slow kinetics of aberrant misfolding and self-assembly

Murine apolipoprotein serum amyloid A in solution forms a hexamer containing a central channel

Serum amyloid A (SAA) is a small apolipoprotein that binds to high-density lipoproteins in the serum. Although SAA seems to play a role in host defense and lipid transport and metabolism, its specific functions have not been defined. Despite the growing implications that SAA plays a role in the pathology of various diseases, a high-resolution structure of SAA is lacking because of limited solubility in the high-density lipoprotein-free form. In this study, complementary methods including glutaraldehyde cross-linking, size-exclusion chromatography, and sedimentation-velocity analytical ultracentrifugation were used to show that murine SAA2.2 in aqueous solution exists in a monomer–hexamer equilibrium. Electron microscopy of hexameric SAA2.2 revealed that the subunits are arranged in a ring forming a putative central channel. Limited trypsin proteolysis and mass spectrometry analysis identified a significantly protease-resistant SAA2.2 region comprising residues 39–86. The isolated 39–86 SAA2.2 fragment did not hexamerize, suggesting that part of the N terminus is involved in SAA2.2 hexamer formation. Circular-dichroism spectrum deconvolution and secondary-structure prediction suggest that SAA2.2 contains ≈50% of its residues in α-helical conformation and <10% in β-structure. These findings are consistent with the recent discovery that human SAA1.1 forms a membrane channel and have important implications for understanding the 3D structure, multiple functions, and pathological roles of this highly conserved protein