Alterations of skeletal muscle bioenergetics in a mouse with F508del mutation leading to a cystic fibrosis-like condition.

Alterations of skeletal muscle bioenergetics in a mouse with F508del mutation leading to a cystic fibrosis-like condition. Am J Physiol Endocrinol Metab. 2019 Jun 18;: Authors: Lai N, Kummitha C, Drumm M, Hoppel C Abstract High energy expenditure is reported in cystic fibrosis (CF) animal models and patients. Alterations in skeletal muscle oxidative capacity, fuel utilization, and creatine kinase-phosphocreatine system suggest mitochondrial dysfunction. Studies were performed on congenic C57BL/6J and F508del (Cftrtm1kth) mice. Indirect calorimetry was used to measure gas exchange to evaluate aerobic capacity during treadmill exercise. The bioenergetic function of skeletal muscle subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria was evaluated using an integrated approach combining measurement of the rate of oxidative phosphorylation by polarography and of electron transport chain activities by spectrophotometry. CF mice have reduced maximal aerobic capacity. In SSM of these mice, oxidative phosphorylation was impaired in the presence of complex I, II, III, and IV substrates except when glutamate was used as substrate. This impairment appeared to be caused by a defect in complex V activity, whereas the oxidative system of the electron transport chain was unchanged. In IFM, oxidative phosphorylation and electron transport chain activities were preserved, whereas complex V activity was reduced in CF. Furthermore, creatine kinase activity was reduced...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research

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Authors: Maiuri L, Raia V, Piacentini M, Tosco A, Villella VR, Kroemer G Abstract Cystic Fibrosis (CF) is the most frequent lethal monogenetic disease affecting humans. CF is characterized by mutations in cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel whose malfunction triggers the activation of transglutaminase-2 (TGM2), as well as the inactivation of the Beclin-1 (BECN1) complex resulting in disabled autophagy. CFTR inhibition, TGM2 activation and BECN1 sequestration engage in an 'infernal trio' that locks the cell in a pro-inflammatory state through anti-homeostatic feedforward lo...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Condition:   Confirmed Diagnosis of Cystic Fibrosis Intervention:   Other: no intervention Sponsors:   University Hospital Inselspital, Berne;   University Children's Hospital, Zurich;   Centre Hospitalier Universitaire Vaudois;   Kantonsspital Aarau;   University Children's Hospital Basel Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
SAN JOSE, Calif., July 19, 2019 -- (Healthcare Sales &Marketing Network) -- Aridis Pharmaceuticals, Inc. (Nasdaq: ARDS) announced today that the European Medicines Agency (EMA) has granted Orphan Drug Designation to AR-501, the Company's inhaled formulat... Biopharmaceuticals, Regulatory Aridis Pharmaceuticals, gallium citrate, cystic fibrosis
Source: HSMN NewsFeed - Category: Pharmaceuticals Source Type: news
FRIDAY, July 19, 2019 -- For patients with cystic fibrosis (CF), ivacaftor use is associated with a reduction in pathogens, including Pseudomonas aeruginosa, according to a study published online July 19 in the Annals of the American Thoracic...
Source: Drugs.com - Pharma News - Category: Pharmaceuticals Source Type: news
5T polymorphism is a CFTR mutation with unclear clinical consequences: the phenotype varies from healthy individuals to Cystic Fibrosis (CF). The aim of this study was to evaluate if nasal potential difference (NPD) and sweat testing correlate with symptoms and CF diagnosis in 5T patients.
Source: Journal of Cystic Fibrosis - Category: Respiratory Medicine Authors: Tags: Original Article Source Type: research
Notice NOT-DK-19-023 from the NIH Guide for Grants and Contracts
Source: NIH Funding Opportunities (Notices, PA, RFA) - Category: Research Source Type: funding
Conditions:   Cystic Fibrosis;   Nontuberculous Mycobacterium Infection Intervention:   Other: Epidemiologic investigation Sponsors:   National Jewish Health;   Cystic Fibrosis Foundation Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Source: ScienceNOW - Category: Science Authors: Tags: Medicine, Diseases perspective Source Type: news
Source: ScienceNOW - Category: Science Authors: Tags: twis Source Type: news
We examined the safety and efficacy of aerosolized xylitol use for 2  weeks in subjects hospitalized with a pulmonary exacerbation of CF.
Source: Journal of Cystic Fibrosis - Category: Respiratory Medicine Authors: Tags: Original Article Source Type: research
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