Polarized distribution of inducible nitric oxide synthase regulates activity in intestinal epithelial cells.
Inducible nitric oxide synthase (iNOS) functions as a homodimer. In cell extracts, iNOS molecules partition both in cytosolic and particulate fractions, indicating that iNOS exists as soluble and membrane associated forms. In this study, iNOS features were investigated in human intestinal epithelial cells stimulated with cytokines and in duodenum from mice exposed to flagellin. Our experiments indicate that iNOS is mainly associated with the particulate fraction of cell extracts. Confocal microscopy showed a preferential localization of iNOS at the apical pole of intestinal epithelial cells. In particulate fractions, iNOS dimers were more abundant than in the cytosolic fraction. Similar observations were seen in mouse duodenum samples. These results suggest that, in epithelial cells, iNOS activity is regulated by localization-dependent processes.
Rumbo
Martin
M
Swiss Experimental Cancer Research Center, Epalinges, Switzerland.
Courjault-Gautier
Françoise
F
Sierro
Frédéric
F
Sirard
Jean-Claude
JC
Felley-Bosco
Emanuela
E
D000818:Animals; D002478:Cells, Cultured; D019281:Dimerization; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II
C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse