Muscle Quality is More Impaired in Sarcopenic Patients With Chronic Obstructive Pulmonary Disease.

Background: Quadriceps muscle fiber atrophy and a loss of oxidative type I muscle fibers and mitochondrial content often occur in chronic obstructive pulmonary disease (COPD), which adversely affects exercise performance. Sarcopenia is an age-related syndrome characterized by wasting and weakness of muscle mass. We recently showed in a large cohort of patients that COPD-related sarcopenia, in particular in male patients, was not only associated with impaired quadriceps muscle strength but also with decreased exercise performance endurance, which could imply involvement of altered muscle fiber type composition.

Alterations in Skeletal Muscle Oxidative Phenotype in Mice Exposed to 3 Weeks of Normobaric Hypoxia.

Skeletal muscle of patients with chronic respiratory failure is prone to loss of muscle mass and oxidative phenotype. Tissue hypoxia has been associated with cachexia and emphysema in humans. Experimental research on the role of hypoxia in loss of muscle oxidative phenotype, however, has yielded inconsistent results.

Hypoxia differentially regulates muscle oxidative fiber type and metabolism in a HIF-1α-dependent manner.

Loss of skeletal muscle oxidative fiber types and mitochondrial capacity is a hallmark of chronic obstructive pulmonary disease and chronic heart failure. Based on in vivo human and animal studies, tissue hypoxia has been hypothesized as determinant, but the direct effect of hypoxia on muscle oxidative phenotype remains to be established. Hence, we determined the effect of hypoxia on in vitro cultured muscle cells, including gene and protein expression levels of mitochondrial components, myosin isoforms (reflecting slow-oxidative versus fast-glycolytic fibers), and the involvement of the regulatory PPAR/PGC-1α pathway.

The muscle oxidative regulatory response to acute exercise is not impaired in less advanced COPD despite a decreased oxidative phenotype.

Already in an early disease stage, patients with chronic obstructive pulmonary disease (COPD) are confronted with impaired skeletal muscle function and physical performance due to a loss of oxidative type I muscle fibers and oxidative capacity (i.e. oxidative phenotype; Oxphen).

Heterogeneity of quadriceps muscle phenotype in chronic obstructive pulmonary disease (Copd); implications for stratified medicine?

Introduction: Quadriceps muscle dysfunction is common in COPD. Determining, and, if possible, predicting quadriceps phenotype in COPD is important for patient stratification for therapeutic trials.

Methods: In biopsies from 114 COPD patients and 30 controls, we measured fiber size and proportion and assessed the relationship with quadriceps function (strength and endurance), clinical phenotype (lung function, physical activity, fat-free mass) and exercise performance.

Pathways associated with reduced quadriceps oxidative fibres and endurance in COPD.

Reduced quadriceps endurance in chronic obstructive pulmonary disease (COPD) is associated with a predominance of type II glycolytic fibres over type I oxidative fibres (fibre shift) and reduced muscle energy stores. The molecular mechanisms responsible for this remain unknown. We hypothesised that expression of known regulators of type I fibres and energy production in quadriceps muscle would differ in COPD patients with and without fibre shift.

Loss of quadriceps muscle oxidative phenotype and decreased endurance in patients with mild-to-moderate COPD.

Being well-established in advanced chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction and its underlying pathology have been scarcely investigated in patients with mild-to-moderate airflow obstruction. We hypothesized that a loss of oxidative phenotype (oxphen) associated with decreased endurance is present in the skeletal muscle of patients with mild-to-moderate COPD. In quadriceps muscle biopsies from 29 patients with COPD (forced expiratory volume in 1 s [FEV1] 58 ± 16%pred, body mass index [BMI] 26 ± 4 kg/m(2)) and 15 controls (BMI 25 ± 3 kg/m(2)) we assessed fiber type distribution, fiber cross-sectional areas (CSA), oxidative and glycolytic gene expression, OXPHOS protein levels, metabolic enzyme activity, and levels of oxidative stress markers.

Galactonolactone oxidoreductase from Trypanosoma cruzi employs a FAD cofactor for the synthesis of vitamin C.

Trypanosoma cruzi, the aetiological agent of Chagas' disease, is unable to salvage vitamin C (l-ascorbate) from its environment and relies on de novo synthesis for its survival. Because humans lack the capacity to synthesize ascorbate, the trypanosomal enzymes involved in ascorbate biosynthesis are interesting targets for drug therapy. The terminal step in ascorbate biosynthesis is catalyzed by flavin-dependent aldonolactone oxidoreductases belonging to the vanillyl-alcohol oxidase (VAO) protein family.