S-nitrosylation of proteins at the leading edge of migrating trophoblasts by inducible nitric oxide synthase promotes trophoblast invasion

Harris, L. K., McCormick, J., Cartwright, J. E., Whitley, G. S. and Dash, P. R. (2008) S-nitrosylation of proteins at the leading edge of migrating trophoblasts by inducible nitric oxide synthase promotes trophoblast invasion. Exp Cell Res, 314 (8). pp. 1765-76. ISSN 0014-4827 doi: 10.1016/j.yexcr.2008.02.010

Abstract/Summary

Nitric oxide regulates many important cellular processes including motility and invasion. Many of its effects are mediated through the modification of specific cysteine residues in target proteins, a process called S-nitrosylation. Here we show that S-nitrosylation of proteins occurs at the leading edge of migrating trophoblasts and can be attributed to the specific enrichment of inducible nitric oxide synthase (iNOS/NOS2) in this region. Localisation of iNOS to the leading edge is co-incidental with a site of extensive actin polymerisation and is only observed in actively migrating cells. In contrast endothelial nitric oxide synthase (eNOS/NOS3) shows distribution that is distinct and non-colocalised with iNOS, suggesting that the protein S-nitrosylation observed at the leading edge is caused only by iNOS and not eNOS. We have identified MMP-9 as a potential target for S-nitrosylation in these cells and demonstrate that it co-localises with iNOS at the leading edge of migrating cells. We further demonstrate that iNOS plays an important role in promoting trophoblast invasion, which is an essential process in the establishment of a successful pregnancy.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/9799
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Uncontrolled Keywords	Cell Line, *Cell Movement, Cysteine/metabolism, Cytoplasm/enzymology, Humans, Matrix Metalloproteinase 9/analysis, Microfilaments/enzymology, Nitric Oxide/*metabolism, Nitric Oxide Synthase Type II/analysis/*metabolism, Nitric Oxide Synthase Type III/analysis, *Protein Processing, Post-Translational, Trophoblasts/*enzymology/physiology
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