RESUMO

A Disintegrin And Metalloprotease 23 (ADAM23) is a member of the ADAMs family of transmembrane proteins, mostly expressed in nervous system, and involved in traffic and stabilization of Kv1-potassium channels, synaptic transmission, neurite outgrowth, neuronal morphology and cell adhesion. Also, ADAM23 has been linked to human pathological conditions, such as epilepsy, cancer metastasis and cardiomyopathy. ADAM23 functionality depends on the molecule presence at the cell surface and along the secretory pathway, as expected for a cell surface receptor. Because endocytosis is an important functional regulatory mechanism of plasma membrane receptors and no information is available about the traffic or turnover of non-catalytic ADAMs, we investigated ADAM23 internalization, recycling and half-life properties. Here, we show that ADAM23 undergoes constitutive internalization from the plasma membrane, a process that depends on lipid raft integrity, and is redistributed to intracellular vesicles, especially early and recycling endosomes. Furthermore, we observed that ADAM23 is recycled from intracellular compartments back to the plasma membrane and thus has longer half-life and higher cell surface stability compared with other ADAMs. Our findings suggest that regulation of ADAM23 endocytosis/stability could be exploited therapeutically in diseases in which ADAM23 is directly involved, such as epilepsy, cancer progression and cardiac hypertrophy.

Assuntos

Proteínas ADAM/metabolismo , Endocitose , Membrana Celular/metabolismo , Células Cultivadas , Endossomos/metabolismo , Meia-Vida , Humanos , Microdomínios da Membrana/metabolismo

RESUMO

BACKGROUND: It remains unclear how closely the physical inactivity observed in patients with Chronic Obstructive Pulmonary Disease (COPD) relates to the severity of their airflow limitation. Furthermore, it is unknown whether spirometric variables such as maximal voluntary ventilation (MVV) and inspiratory capacity (IC) reflect the level of physical activity in daily life better than the forced expiratory volume in the first second (FEV(1)), the main spirometric variable used to determine the severity of COPD. The objective of the present study was to investigate the relationship between physical activity in daily life and the severity of COPD assessed by different spirometric variables: MVV, IC and FEV(1). METHODS: Forty patients with COPD (21 men; 68+/-7 years; FEV(1) 41+/-14% predicted) were performed spirometry and assessment of the physical activity level in daily life using an accelerometer (SenseWear Armband). RESULTS: MVV was significantly correlated to total energy expenditure per day, energy expenditure per day in activities demanding more than 3 metabolic equivalents (METs), number of steps per day and time spent per day in moderate and vigorous activities (0.42

Assuntos

Atividade Motora , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ventilação Pulmonar , Atividades Cotidianas , Idoso , Metabolismo Energético , Volume Expiratório Forçado , Humanos , Capacidade Inspiratória , Ventilação Voluntária Máxima , Pessoa de Meia-Idade , Espirometria/métodos , Capacidade Vital