RESUMEN
Dietary methionine restriction (MR) has been found to affect one of the most primary tissue-level functions of an organism: the efficiency with which the epithelial linings of major organs separate the fluid compartments that they border. This process, epithelial barrier function, is basic for proper function of all organs, including the lung, liver, gastrointestinal tract, reproductive tract, blood-brain barrier, and kidney. Specifically, MR has been found to modify the protein composition of tight junctional complexes surrounding individual epithelial cells in a manner that renders the complexes less leaky. This has been observed in both a renal epithelial cell culture model and in gastrointestinal tissue. In both cases, MR increased the transepithelial electrical resistance across the epithelium, while decreasing passive leak of small nonelectrolytes. However, the specific target protein modifications involved were unique to each case. Overall, this provides an example of the primary level on which MR functions to modify, and improve, an organism.
Asunto(s)
Restricción Calórica , Epitelio/fisiología , Salud , Metionina/metabolismo , Aminoácidos Sulfúricos/metabolismo , Animales , Transporte Biológico , Susceptibilidad a Enfermedades , Humanos , Micronutrientes/metabolismo , Ocludina/metabolismo , Permeabilidad , Uniones Estrechas/metabolismo , Uniones Estrechas/patologíaRESUMEN
The relative abundance of various claudin proteins of LLC-PK(1) renal epithelial tight junctions (TJs) is modulated by culturing the cells in a medium that is sharply reduced in the sulfur-containing amino acids, cysteine, cystine, and methionine. The functional result is an epithelial barrier that has a higher transepithelial electrical resistance and a decreased paracellular leak to D-mannitol (i.e., improved barrier function). This is accomplished without affecting the culture's confluent cell density, its short circuit current, or its hallmark differentiated property, Na(+)-dependent sugar transport. The implications of being able to enhance epithelial TJ barrier function by nutritional means are discussed, particularly in light of the ability of methionine-restrictive diets to enhance life span and forestall age-related morbidity.
Asunto(s)
Uniones Estrechas/metabolismo , Uniones Estrechas/ultraestructura , Animales , Restricción Calórica , Recuento de Células , Permeabilidad de la Membrana Celular , Polaridad Celular , Conductividad Eléctrica , Impedancia Eléctrica , Células Epiteliales/metabolismo , Túbulos Renales Proximales/metabolismo , Células LLC-PK1 , Metionina/metabolismo , Modelos Biológicos , PorcinosRESUMEN
Gene expression is known to change during development and to vary among genetically diverse strains. Previous studies of temporal patterns of gene expression during C. elegans development were incomplete, and little is known about how these patterns change as a function of genetic background. We used microarrays that comprehensively cover known and predicted worm genes to compare the landscape of genetic variation over developmental time between two isolates of C. elegans. We show that most genes vary in expression during development from egg to young adult, many genes vary in expression between the two isolates, and a subset of these genes exhibit isolate-specific changes during some developmental stages. This subset is strongly enriched for genes with roles in innate immunity. We identify several novel motifs that appear to play a role in regulating gene expression during development, and we propose functional annotations for many previously unannotated genes. These results improve our understanding of gene expression and function during worm development and lay the foundation for linkage studies of the genetic basis of developmental variation in gene expression in this important model organism.