Polarized distribution of inducible nitric oxide synthase regulates activity in intestinal epithelial cells

RUMBO M, COURJAULT-GAUTIER F., SIERRO F., SIRARD J.C.AND FELLEY-BOSCO

FEBS JOURNAL

Año: 2005 vol. 272 p. 444 - 453

1742-464X

Inducible nitric oxide synthase (iNOS) functions as a homodimer and partitions both in cytosolic and particulate fraction. In this study, iNOS activity was assessed in human intestinal epithelial cells stimulated with cytokines- or duodenum tissue from mice exposed to flagellin. First, we found that iNOS is mainly associated to the particulate fraction in polarized intestinal epithelial cells. Confocal microscopy showed that this correlates with the preferential apical localization of iNOS. In addition, gel filtration chromatography allowed to determine that bioactive iNOS dimers are more abundant in the particulate that in the cytosolic fraction. The same observations were derived from duodenum samples of mice exposed to flagellin. These results indicate a new mechanism of regulation of iNOS activity relying on a localization-dependent process and provide tools for further investigation of the mechanisms involved in this differential iNOS dimer distribution.