The nNOS Gene

Diversity appears to represent a major theme evident upon analysis of human nNOS mRNA transcripts. This diversity is both structural and allelic. Cassette deletions of exons 9/10 and 10 have been demonstrated in various 

---

A recent study showed significant increases of expression of eNOS in the brains of rats treated with pyrithia-mine [20]. Increased eNOS expression was apparent prior to the onset of neurological symptoms and was restricted to vulnerable medial thalamus and inferior colliculus. Expression of inducible (iNOS) and neuronal (nNOS) isoforms were minimally altered in brain in thiamine deficiency and it has also been shown that targeted disruption of the eNOS (but not the iNOS or nNOS) gene results in reduced extent of neuropathological damage in thalamus of thiamine deficient animals [21] (Fig. 34-5). 

Moreover, targeted disruption (knock-down) of the eNOS gene attenuates the neuronal cell death in thiamine-deficient mice (Gibson and Zhang, 2002). eNOS knock-down but not knock-down of iNOS or nNOS leads to a reduction in protein tyrosine nitration (Beauchesne et al., 2009), suggesting a major role of eNOS as the source of nitric oxide-related nitrosative stress in thiamine deficiency. 

Levecque C, Elbaz A, Clavel J, Richard F, Vidal JS, Amouyel P, Tzourio C, Alperovitch A, Chartier-Harlin MC (2003) Association between Parkinson s disease and polymorphisms in the nNOS and iNOS genes in a community-based case-control study. Hum Mol Genet 12 79-86. 

Ananth C., Dheen S. T., Gopalakrishnakone R, and Kaur C. (2003a). Distribution of NADPH-diaphorase and expression of nNOS, N-methyl-D-aspartate receptor (NMDARl) and non-NMDA glutamate receptor (GlutR2) genes in the neurons of the hippocampus after domoic acid-induced lesions in adult rats. Hippocampus 13 260-272. 

In mammals, the biosynthesis of NO is catalysed by the enzyme NOS. So far, three isoenzymes that represent distinct gene products have been identified the inducible (iNOS) isoform, the constitutive endothelial (eNOS) isoform and the constitutive neuronal (nNOS) isoform (table I). Comparison of the respective amino acid sequences shows that these three isoforms are about 50-60% identical (for review see [35]). 

The body has three different tissue-specific isoforms of NO synthase, each encoded by a different gene neuronal nitric oxide synthase (nNOS, isoform I), inducible nitric oxide synthase (iNOS, isoform II), and endothelial nitric oxide synthase (eNOS, isoform III). nNOS and eNOS are tightly regulated by Ca concentration to produce the small amounts of NO required for its role as a neurotransmitter and hormone. In contrast, iNOS is present in many cells of the immune system and cell types with a similar lineage, such as macrophages and... 

---