Modification of tight junction structure and permeability by nutritional means.
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.
Mullin
James M
JM
Lankenau Institute for Medical Research, Princeton University, Wynnewood, PA 19096, USA. mullinj@mlhs.org
Skrovanek
Sonja M
SM
Valenzano
Mary Carmen
MC
D000818:Animals; D031204:Caloric Restriction; D002452:Cell Count; D002463:Cell Membrane Permeability; D016764:Cell Polarity; D004553:Electric Conductivity; D017097:Electric Impedance; D004847:Epithelial Cells / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D018374:LLC-PK1 Cells; D008715:Methionine / Q000378:metabolism; D008954:Models, Biological; D013552:Swine; D019108:Tight Junctions / Q000378:metabolism* / Q000648:ultrastructure*
D008715:Methionine