Nitric oxide signal transduction function

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

Schmidt, H.H., Gagne, G.D., Nakane, M. etal. (1992). Mapping of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase, and novel paraneural functions for nitrinergic signal transduction. J. Histochem. Cytochem. 40, 1439-1456. 

In addition to antioxidant activity, there are specific a-tocopherol-dependent functions that normalize cellular functions in a variety of cells. a-Tocopherol plays a critical role through its ability to inhibit the activity of protein kinase C, a central player in many signal transduction pathways. Specifically, it modulates pathways of platelet aggregation, endothelial cell nitric oxide production, monocyte/macrophage superoxide production, and smooth muscle cell proliferation. Regulation of adhesion molecule expression and inflammatory cell cytokine production by a-tocopherol has also been reported. However, most of the information in this area has been obtained from in vitro studies. More studies in hiunans are needed to relate a-tocopherol intakes and tissue concentrations to optimal tissue responses. 

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