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Mullin JM, Skrovanek SM, Valenzano MC: Modification of tight junction structure and permeability by nutritional means. Ann N Y Acad Sci. 2009 May;1165:99-112. 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. |
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