Preeclampsia complicates 5-8% of all pregnancies worldwide, and although its pathophysiology remains obscure, placental oxidative stress mitochondrial abnormalities are considered to play a key role. Mitochondrial in preeclamptic placentae have been described, but the extent which content molecular pathways controlling this (mitochondrial biogenesis mitophagy) affected is unknown. Therefore, (n = 12) control 11) placentae, we comprehensively assessed multiple indices antioxidant status,...

Introduction Impaired utero-placental perfusion is a well-known feature of early preeclampsia and associated with placental hypoxia oxidative stress. Although aberrations at the level mitochondrion have been implicated in PE pathophysiology, whether or not hypoxia-induced mitochondrial abnormalities contribute to stress unknown. Methods We explored metabolism by using both healthy term placentae as well trophoblast cell line (BeWo cells) exposed hypoxia. Furthermore, we therapeutic potential...

Physical inactivity significantly contributes to loss of muscle mass and performance in bed-bound patients. Loss skeletal mitochondrial content has been well-established unloading models, but the underlying molecular mechanism remains unclear. We hypothesized that apparent unloading-induced is preceded by increased mitophagy- decreased biogenesis-signaling during early stages unloading.We analyzed a comprehensive set markers involved mitochondrial-autophagy, -biogenesis, -dynamics, -content,...

Loss of skeletal muscle mitochondrial oxidative capacity is well-established in patients with COPD, but the role breakdown herein largely unexplored. Currently, we studied if signalling increased COPD and associates loss content, whether it affected iron deficiency (ID) or systemic inflammation. Therefore, mitophagy, autophagy, dynamics content markers were analysed vastus lateralis biopsies (N = 95, FEV1% predicted: 39.0 [31.0-53.6]) healthy controls 15, 112.8 [107.5-125.5]). Sub-analyses...

Iron homeostasis is essential for mitochondrial function, and iron deficiency has been associated with skeletal muscle weakness decreased exercise capacity in patients different chronic disorders. We hypothesized that deficiency-induced loss of mitochondria caused by increased clearance. To study this, C2C12 myotubes were subjected to the chelator deferiprone. Mitochondrial parameters key constituents mitophagy pathways studied presence or absence pharmacological autophagy inhibition...

Calciprotein particles (CPPs) provide an efficient mineral buffering system to prevent the complexation of phosphate and calcium in circulation. However, chronic kidney disease (CKD), load exceeds capacity, resulting formation crystalline CPP2 particles. have been associated with cardiovascular events mortality. Moreover, demonstrated induce calcification vitro. In this study, we examined fate a rat model CKD. Calcification was induced Sprague-Dawley rats by 5/6 nephrectomy (5/6-Nx) combined...

Exposure of the airways to cigarette smoke (CS) is primary risk factor for developing several lung diseases such as Chronic Obstructive Pulmonary Disease (COPD). CS consists a complex mixture over 6000 chemicals including highly reactive α,β-unsaturated aldehyde acrolein. Acrolein thought be responsible large proportion non-cancer disease associated with smoking. Emerging evidence suggest key role CS-induced abnormalities in mitochondrial morphology and function airway epithelial cells COPD...

Abstract Background Pulmonary rehabilitation (PR) is a cornerstone in the management of chronic obstructive pulmonary disease (COPD), targeting skeletal muscle to improve functional performance. However, there substantial inter‐individual variability effect PR on performance, which cannot be fully accounted for by generic phenotypic factors. We performed an unbiased integrative analysis molecular responses COPD patients and comprehensively characterized their baseline physical function, body...

Activation of skeletal muscle contractions require that action potentials can be excited and propagated along the fibers. Recent studies have revealed fiber excitability is regulated during repeated firing by cellular signaling systems control function ion channel determine resting membrane conductance (Gm). In fast-twitch muscle, prolonged triggers a marked increase in Gm, reducing causing potential failure. Both ClC-1 KATP channels contribute to this Gm rise, but exact molecular regulation...

Abstract Abnormal mitochondria have been observed in bronchial- and alveolar epithelial cells of patients with chronic obstructive pulmonary disease (COPD). However, it is unknown if alterations the molecular pathways regulating mitochondrial turnover (mitochondrial biogenesis vs mitophagy) are involved. Therefore, this study, abundance key molecules controlling were assessed peripheral lung tissue from non-COPD (n = 6) COPD 11; GOLDII n 4/11; GOLDIV 7/11) both undifferentiated...

Skeletal muscle regeneration after disuse is essential for maintenance and involves the regulation of both mass- metabolic plasticity-related processes. However, relation between these processes during recovery from remains unclear. In this study, we explored potential interrelationship molecular mass oxidative metabolism disuse. Molecular profiles were measured in biopsies vastus lateralis healthy men 1-leg cast immobilization 1 wk reloading, mouse gastrocnemius obtained before hindlimb...

Abstract Digestion of dietary fibers by gut bacteria has been shown to stimulate intestinal mineral absorption [e.g., calcium (Ca 2+ ) and magnesium (Mg )]. Although it suggested that local pH short-chain fatty acid (SCFA) concentrations determine divalent cation absorption, the exact molecular mechanisms are still unknown. Therefore, this study aimed effects SCFAs on Mg absorption. We show butyrate concentration in colon negatively correlates with serum levels wildtype mice. Moreover,...

Both mitophagy, a selective mechanism for clearance of mitochondria, and mitochondrial biogenesis are key processes determining content oxidative capacity the musculature. Abnormalities in these could therefore contribute to deterioration peripheral muscle as observed e.g. chronic obstructive pulmonary disease. Although it has been suggested that inflammatory mediators can modulate both mitophagy biogenesis, is unknown whether acute inflammation affects glycolytic skeletal vivo. Therefore,...

<b>Background:</b> Pulmonary rehabilitation (PR) is a cornerstone in the management of COPD, targeting skeletal muscle to improve exercise performance. However, there substantial inter-individual variability effect PR on performance, which cannot be fully accounted for by generic phenotypic factors. To identify groups with differential response, we performed an unbiased integrative analysis molecular responses COPD patients. <b>Methods:</b><i>M. Quadriceps</i> biopsies were obtained from 51...

Nowadays, mitochondria are recognized as key players in the pathogenesis of a variety smoking-associated lung diseases. Acrolein, component cigarette smoke, is known driver biological mechanisms underlying smoking-induced respiratory toxicity. The impact sub-acute acrolein inhalation vivo on processes controlling mitochondrial homeostasis cells airways however unknown. In this study, we investigated activity/abundance myriad molecules critically involved metabolic pathways and quality...

<b>Objective:</b> Systemic inflammation has been implicated in skeletal muscle mitochondrial impairment of patients with COPD. Both mitophagy, a selective clearance mechanism, and biogenesis are required for homeostasis. We hypothesized that inflammation-induced loss capacity is associated decreased increased mitophagy. <b>Methods:</b> Mice were subjected to single intratracheal instillation lipopolysaccharide (IT-LPS) or NaCl. On several time-points post IT-LPS, (<i>m. gastrocnemius</i>)...

<b>Objective:</b> COPD is hallmarked by a loss of skeletal muscle oxidative capacity which already present in less advanced disease stages. In this study, we hypothesized that mitophagy (selective mitochondrial autophagy) enhanced patients, and associated with the capacity. <b>Methods:</b><i>Vastus lateralis</i> biopsies were taken patients mild-to-moderate airflow obstruction (FEV₁ %pred=57.2(46.8,68.2), n=29) healthy controls %pred=112.8(107.5;125.5), n=15). Oxidative was...

<b>Background:</b> The prevalence of sarcopenia is high in advanced COPD. Although muscle atrophy an imbalance between anabolism and catabolism evident, data on regulation protein turnover COPD conflicting. Therefore, we studied molecular signatures a large, well-phenotyped cohort. <b>Methods:</b> Quadriceps biopsies were obtained from 91 patients 14 healthy control subjects (C), recruited Maastricht (NLD) Golnik (SLV). Sarcopenia was assessed by DEXA. Protein mRNA levels regulatory...

Loss of skeletal muscle mitochondrial content is an important extra-pulmonary manifestation COPD, which the cause only partly understood. Pre-clinical research indicates that systemic inflammation induces breakdown (mitophagy). Hence, we hypothesise COPD patients characterized by exhibits a pro-mitophagy gene and protein expression profile associated with loss content. Vastus lateralis biopsies were obtained patients, high sensitive serum C-reactive (CRP) levels determined ELISA as marker...

Abstract Introduction/Aims Both neuromuscular junction (NMJ) dysfunction and altered electrophysiological properties of muscle fibers have been reported in amyotrophic lateral sclerosis (ALS) patients. ALS‐related preclinical studies typically use rodent SOD1 G93A overexpression models, but translation to the human disease has challenged. The present work explored NMJ function cellular muscles rats. Methods Longitudinal compound action potentials (CMAPs) were performed Cellular evaluate...