Person: Cruz Rodríguez, Antonio
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First Name
Antonio
Last Name
Cruz Rodríguez
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Químicas
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
Identifiers
3 results
Search Results
Now showing 1 - 3 of 3
Item Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia(Scientific Reports, 2020) Autilio, Chiara; Echaide Torreguitar, Mercedes; Cruz Rodríguez, Antonio; Hidalgo, A.; Da Silva, E.; De Luca, Daniele; Sørli, Jorid B.; Pérez-Gil, JesúsTherapeutic hypothermia (TH) enhances pulmonary surfactant performance in vivo by molecular mechanisms still unknown. Here, the interfacial structure and the composition of lung surfactant flms have been analysed in vitro under TH as well as the molecular basis of its improved performance both under physiological and inhibitory conditions. The biophysical activity of a purifed porcine surfactant was tested under slow and breathing-like dynamics by constrained drop surfactometry (CDS) and in the captive bubble surfactometer (CBS) at both 33 and 37 °C. Additionally, the temperaturedependent surfactant activity was also analysed upon inhibition by plasma and subsequent restoration by further surfactant supplementation. Interfacial performance was correlated with lateral structure and lipid composition of flms made of native surfactant. Lipid/protein mixtures designed as models to mimic diferent surfactant contexts were also studied. The capability of surfactant to drastically reduce surface tension was enhanced at 33 °C. Larger DPPC-enriched domains and lower percentages of less active lipids were detected in surfactant flms exposed to TH-like conditions. Surfactant resistance to plasma inhibition was boosted and restoration therapies were more efective at 33 °C. This may explain the improved respiratory outcomes observed in cooled patients with acute respiratory distress syndrome and opens new opportunities in the treatment of acute lung injury.Item Biophysical and biological impact on the structure and IgE-binding of the interaction of the olive pollen allergen Ole e 7 with lipids(Biochimica et Biophysica Acta (BBA) - Biomembranes, 2020) Oeo-Santos, Carmen; López Rodríguez, Juan Carlos; García Mouton, Cristina; San Segundo Acosta, Pablo; Jurado, Aurora; Moreno-Aguilar, Carmen; García Álvarez, María Begoña; Pérez Gil, Jesús; Villalba Díaz, María Teresa; Barderas Manchado, Rodrigo; Cruz Rodríguez, AntonioOle e 7 allergen from Olea europaea pollen possesses a major clinical relevance because it produces severe symptoms, such as anaphylaxis, in allergic patients exposed to high olive pollen counts. Ole e 7 is a non-specific lipid transfer protein (nsLTP) characterized by the presence of a tunnel-like hydrophobic cavity, which may be suitable for hosting and, thus, transporting lipids -as it has been described for other nsLTPs-. The identification of the primary amino acid sequence of Ole e 7, and its production as a recombinant allergen, allowed characterizing its lipid-binding properties and its effect at air-liquid interfaces. Fluorescence and interferometry experiments were performed using different phospholipid molecular species and free fatty acids to analyse the lipid-binding ability and specificity of the allergen. Molecular modelling of the allergen was used to determine the potential regions involved in lipid interaction. Changes in Ole e 7 structure after lipid interaction were analysed by circular dichroism. Changes in the IgE binding upon ligand interaction were determined by ELISA. Wilhelmy balance measurements and fluorescence surfactant adsorption tests were performed to analyse the surface activity of the allergen. Using these different approaches, we have demonstrated the ability of Ole e 7 to interact and bind to a wide range of lipids, especially negatively charged phospholipids and oleic acid. We have also identified the protein structural regions and the residues potentially involved in that interaction, suggesting how lipid-protein interactions could define the behaviour of the allergen once inhaled at the airways.Item The lord of the Lungs: the essential role of pulmonary surfactant upon inhalation of nanoparticles(European Journal of Pharmaceutics and Biopharmaceutics, 2019) García-Mouton, Cristina; Hidalgo Román, Alberto; Cruz Rodríguez, Antonio; Pérez-Gil, JesúsThe rapid development of nanotechnology is opening a huge world of promising possibilities in healthcare, but this is also increasing the necessity to study the potential risk of nanoparticles on public health and the environment. Since the main route for airborne particles to enter into our organism is through the lungs, it has become essential to prove that the nanoparticles generated by human activities do not compromise the respiratory function. This review explains the key role of pulmonary surfactant to sustain the normal function of breathing, as well as the stability and immunity of lungs. Particular emphasis is made on the importance of analysing the features of nanoparticles, defining their interactions with surfactant and unravelling the mutual effects. The implication of the nanoparticle-surfactant interaction on the function and fate of both structures is described, as well as the main in vitro methodologies used to evaluate this interaction. Finally, the incorporation of pulmonary surfactant in appropriate in vitro models is used in order to obtain an extensive understanding of how nanoparticles may act in the context of the lung. The main goal of this review is to offer a general view on inhaled nanoparticles and their effects on the structure and function of lungs derived from their interaction with the pulmonary surfactant system.