A New Paradigm

Abstract

See related article, pages 870–877 Caveolae, cholesterol rich microdomain platforms localized mostly at the cytoplasmic membrane of endothelial cells as well as other cell types, are importantly involved in cell signaling and enzymatic activity.1–6 Caveolae also contain cationic amino acid transporter (CAT) which provide L-Arginine to the eNOS-Ca2+-Calmodulin complex toward the production of nitric oxide (NO).1–6 Caveolin-1, a major caveolae-localized protein, represses markedly eNOS-dependent NO production by interfering with NADPH-dependent electron flux.3 Alteration in caveolin abundance or its subcellular location leads to the control of NO production.5,6 Thus, it is clear, that the more the caveolin the less the NO, and inversely.3 The conventional paradigm supports the concept that eNOS–caveolin-1 interaction promotes inhibition of NO production, whereas increased intracellular Ca2+ activates Ca2+-Calmodulin which in turn disrupts the eNOS–caveolin-1 interaction and thus liberates the enzyme. This in turn promotes NO production.1–6 A new paradigm is now suggested by Miniatis and colleagues7, who elegantly demonstrated that NO production in pulmonary endothelial cells is significantly mediated by caveolae internalization and is independent of the increase of intracellular Ca2+. …