RESUMEN
Long-term exposure to hyperglycemic conditions leads to ß-cell dysfunction, particularly mitochondrial dysfunction, and inflammatory and oxidative stress responses, which are considered the primary causes of ß-cell death and the hallmarks of diabetes. Plant-active ingredients may play a key role in glycemic control. Epigallocatechin gallate (EGCG) is a characteristic catechin derived from tea that possesses anti-diabetic properties. Nonetheless, its underlying mechanisms remain elusive. Herein, the protective role of EGCG on high glucose (33 mM)-induced pancreatic beta cell dysfunction and its possible molecular mechanisms were investigated. Briefly, MIN6 cells were treated with glucose and EGCG (10 µM, 20 µM, and 40 µM) for 48 h. Our results revealed that EGCG dose-dependently restored mitochondrial membrane potential and concomitantly alleviated cell apoptosis. Mechanistically, the expression level of apoptotic protein BAX and Dynamic related protein 1 (DRP1) was significantly downregulated following EGCG treatment, whereas that of the anti-apoptotic protein BCL-2 was significantly upregulated. Taken together, EGCG alleviated high glucose-induced pancreatic beta cell dysfunction by targeting the DRP1-related mitochondrial apoptosis pathway and thus can serve as a nutritional intervention for the preservation of beta cell dysfunction in patients with type 2 diabetes mellitus.
Asunto(s)
Apoptosis , Catequina , Dinaminas , Glucosa , Células Secretoras de Insulina , Mitocondrias , Catequina/análogos & derivados , Catequina/farmacología , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Apoptosis/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Glucosa/metabolismo , Dinaminas/metabolismo , Dinaminas/genética , Animales , Ratones , Línea Celular , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismoRESUMEN
Arc-shaped BIN/Amphiphysin/Rvs (BAR) domain proteins generate curvature by binding to membranes and induce membrane tubulation at sufficiently large protein coverages. For the amphiphysin N-BAR domain, Le Roux et al., Nat. Commun. 2021, 12, 6550, measured a threshold coverage of 0.44 ± 0.097 for nanotubules emerging from the supported lipid bilayer. In this article, we systematically investigate membrane tubulation induced by arc-shaped protein-like particles with coarse-grained modeling and simulations and determine the threshold coverages at different particle-particle interaction strengths and membrane spontaneous curvatures. In our simulations, the binding of arc-shaped particles induces a membrane shape transition from spherical vesicles to tubules at a particle threshold coverage of about 0.5, which is rather robust to variations of the direct attractive particle interactions or spontaneous membrane curvature in the coarse-grained model. Our study suggests that threshold coverages of around or slightly below 0.5 are a general requirement for membrane tubulation by arc-shaped BAR domain proteins.
Asunto(s)
Membrana Dobles de Lípidos , Membrana Dobles de Lípidos/química , Membrana Dobles de Lípidos/metabolismo , Simulación de Dinámica Molecular , Dominios Proteicos , Membrana Celular/química , Membrana Celular/metabolismo , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/metabolismoRESUMEN
Integral or peripheral membrane proteins, or protein oligomers often get close to each other on cell membranes and carry out biological tasks in a collective manner. In addition to electrostatic and van der Waals interactions, those proteins also experience membrane-mediated interactions, which may be necessary for their functionality. The membrane-mediated interactions originate from perturbation of lipid membranes by the presence of protein inclusions, and have been the subject of intensive research in membrane biophysics. Here we review both theoretical and numerical studies of such interactions for membrane proteins and for nanoparticles bound to lipid membranes.