Proteins with PDZ domains, such as postsynaptic density-95 (PSD-95), can directly bind to nNOS via PDZ/PDZ interaction. Different from its isoenzymes iNOS and eNOS, the nitrogen terminal of nNOS contains PDZ (spot-synchronous density protein, discs-large, ZO-1) domains, an additional N-terminal extension mostly involved in specific subcellular targeting (Fig. In the central nervous system (CNS), nNOS functions by producing NO and peroxynitrite. nNOS, a Ca 2+-dependent constitutive synthase, is mainly expressed in neurons and is strictly regulated by N-methyl-D-aspartate receptor (NMDAR)-mediated changes in the concentration of intracellular Ca 2+. Three genetically different isoforms of nitric oxide synthase (NOS), namely neuronal NOS (nNOS or NOS-Ι), inducible NOS (iNOS or NOS-II), and endothelial NOS (eNOS or NOS-III), account for nitric oxide (NO) production.
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