Nos1
From Proteopedia
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NOS1 is a major component of the production of Nitric Oxide which Nitric Oxide has important roles in the CNS. Nitric Oxide targets NO receptors on G-cylcase as well as other Nitric Oxide specific receptors. NOS1 is an important component of synaptogenesis, long-term potentiation, neurotransmitter release and synaptic plasticity <ref>Juliane Kopf, Martin Schecklmann, Tim Hahn, Thomas Dresler, Alica C. Dieler, Martin J. Herrmann, Andreas J. Fallgatter, Andreas Reif. (2011) NOS1 ex1f-VNTR polymorphism influences prefrontal brain oxygenation during a working memory task, NeuroImage, Volume 57, (Issue 4),1617-1623, Ihttp://dx.doi.org/10.1016/</ref>.NOS1 is coupled with N-methyl-D-Aspartate (NMDA) receptors in the post-synapse of cells, which allows to the processes to occur. The NMDA receptor binds to PSD95 which than binds to NOS1. After the complex is formed, NDMDA receptor mediated CA2+ influx now regulates the amount of Nitric Oxide is produced by NOS1 <ref>Freudenberg, F., Alttoa, A. & Reif, A. (2015) Neuronal nitric oxide synthase (NOS1) and its adaptor, NOS1AP, as a genetic risk factors for psychiatric. Genes Brain Behav 14, 47–64.</ref>. | NOS1 is a major component of the production of Nitric Oxide which Nitric Oxide has important roles in the CNS. Nitric Oxide targets NO receptors on G-cylcase as well as other Nitric Oxide specific receptors. NOS1 is an important component of synaptogenesis, long-term potentiation, neurotransmitter release and synaptic plasticity <ref>Juliane Kopf, Martin Schecklmann, Tim Hahn, Thomas Dresler, Alica C. Dieler, Martin J. Herrmann, Andreas J. Fallgatter, Andreas Reif. (2011) NOS1 ex1f-VNTR polymorphism influences prefrontal brain oxygenation during a working memory task, NeuroImage, Volume 57, (Issue 4),1617-1623, Ihttp://dx.doi.org/10.1016/</ref>.NOS1 is coupled with N-methyl-D-Aspartate (NMDA) receptors in the post-synapse of cells, which allows to the processes to occur. The NMDA receptor binds to PSD95 which than binds to NOS1. After the complex is formed, NDMDA receptor mediated CA2+ influx now regulates the amount of Nitric Oxide is produced by NOS1 <ref>Freudenberg, F., Alttoa, A. & Reif, A. (2015) Neuronal nitric oxide synthase (NOS1) and its adaptor, NOS1AP, as a genetic risk factors for psychiatric. Genes Brain Behav 14, 47–64.</ref>. | ||
NOS1 also contributes in limiting increased oxidative stress in the myocardium, limits systolic and diastolic dysfunction and all prevent a failing heart. NOS1 regulates the reuptake of Ca2+ in sarcoplamisic reticulum (SR). NOS1is shown into the human coronary artery smooth cells and maintains of basal blood flow. NOS1 also controls the parasympathetic and sympathetic regulation of the heart<ref>Zhang, Y. H., Jin, C. Z., Jang, J. H., & Wang, Y. (2014). Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. The Journal of Physiology, 592(Pt 15), 3189–3200. http://doi.org/10.1113/jphysiol.2013.270306]</ref>. NOS1 is important in all functions that help regulate the cardiac muscles<ref>Zhang, Y. H., Jin, C. Z., Jang, J. H., & Wang, Y. (2014). Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. The Journal of Physiology, 592(Pt 15), 3189–3200. http://doi.org/10.1113/jphysiol.2013.270306]</ref>. The ability of Nitric Oxide to self regulate enables NOS1 to control all these major functions. In myocite relaxation, the Nitric Oxide produced by NOS1 facilitates SERCA to increase intracellular CA2+ because if the increase in PKA dependent PLN phosphorylation. NOS1 also regulates cardiac function by the Nitric Oxide produced targets not CA2+ dependent<ref>Zhang, Y. H., Jin, C. Z., Jang, J. H., & Wang, Y. (2014). Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. The Journal of Physiology, 592(Pt 15), 3189–3200. http://doi.org/10.1113/jphysiol.2013.270306]</ref> | NOS1 also contributes in limiting increased oxidative stress in the myocardium, limits systolic and diastolic dysfunction and all prevent a failing heart. NOS1 regulates the reuptake of Ca2+ in sarcoplamisic reticulum (SR). NOS1is shown into the human coronary artery smooth cells and maintains of basal blood flow. NOS1 also controls the parasympathetic and sympathetic regulation of the heart<ref>Zhang, Y. H., Jin, C. Z., Jang, J. H., & Wang, Y. (2014). Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. The Journal of Physiology, 592(Pt 15), 3189–3200. http://doi.org/10.1113/jphysiol.2013.270306]</ref>. NOS1 is important in all functions that help regulate the cardiac muscles<ref>Zhang, Y. H., Jin, C. Z., Jang, J. H., & Wang, Y. (2014). Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. The Journal of Physiology, 592(Pt 15), 3189–3200. http://doi.org/10.1113/jphysiol.2013.270306]</ref>. The ability of Nitric Oxide to self regulate enables NOS1 to control all these major functions. In myocite relaxation, the Nitric Oxide produced by NOS1 facilitates SERCA to increase intracellular CA2+ because if the increase in PKA dependent PLN phosphorylation. NOS1 also regulates cardiac function by the Nitric Oxide produced targets not CA2+ dependent<ref>Zhang, Y. H., Jin, C. Z., Jang, J. H., & Wang, Y. (2014). Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. The Journal of Physiology, 592(Pt 15), 3189–3200. http://doi.org/10.1113/jphysiol.2013.270306]</ref> | ||
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== Disease == | == Disease == | ||
+ | Nitric oxide (NO) is produced from one of three synthases present within the body: neuronal nitric oxide synthase 1 (NOS1), inducible nitric oxide synthase 2 (NOS2), and endothelial nitric oxide synthase 3 (NOS3) (Shinkai, et. al, 2002). Specifically, NOS1 has nine different first exons that lead to multiple NOS1 transcripts with different 5’-untranslated regions (Galimberti, et. al, 2008). An advantage of having multiple first exons that can be alternatively spliced and expressed is that NOS1 can be specific and specifically regulated for different tissues (Galimberti, et. al, 2008). A disadvantage to having multiple first exons is that there is a higher possibility of mutations, which would affect NO production and thus have an effect on the second messenger cyclic guanine monophosphate (cGMP) production (Shinkai, et. al, 2002). Furthermore, because NO is an oxyradical, overproduction caused by a mutation can lead to neural tissue damage (Shinkai, et. al, 2002). Numerous pathologies may arise from neural tissue damage, and one study suggested overproduction of NO that leads to such damage is possibly an influential factor in developing schizophrenia (Shinkai, et. al, 2002). | ||
+ | Single nucleotide polymorphisms (SNPs) and various lengths of tandem repeats within NOS1 have been linked in other disorders of the brain such as Alzheimer’s and Parkinson’s diseases (Galimberti, et. al, 2008; Rife, et. al, 2009). Out of three identified SNPs occurring in alternative exon 1c, only the SNP G-84A has a functional effect that decreases transcription levels (Galimberti, et. al, 2008). However, various lengths of tandem repeats present in the alternative exon 1f has been shown to be a potential factor in both Alzheimer’s and Parkinson’s diseases (Galimberti, et. al, 2008; Rife, et. al, 2009). Shorter tandem TG repeats are possibly associated with the development of Alzheimer’s disease, and longer tandem TG repeats are possibly associated with the development of Parkinson’s disease (Rife, et. al, 2009). Although schizophrenia, Alzheimer’s, and Parkinson’s diseases have genetic influences, mutations in NOS1 can be a risk indicator for developing these diseases (Shinkai, et. al, 2002; Galimberti, et. al, 2008; Rife, et. al, 2009). | ||
== Relevance == | == Relevance == | ||
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</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
+ | Shinkai, T., Ohmori, O., Hori, H., and Nakamura, J. (2002) Allelic association of the neuronal nitric oxide synthase (NOS1) gene with schizophrenia. Molecular Psychiatry. 7, 560-563. doi:10.1038/sj.mp.4001041 | ||
+ | Galimberti, D., Scarpini, E., Venturelli, E., Strobel, A., Herterich, S., Fenogolio, C., Guidi, I., Scalabrini, D., Cortini, F., Bresolin, N., Lesch, K., and Reif, A. (2008) Association of a NOS1 promoter repeat with Alzheimer’s disease. Neurobiology of Aging. 29, 1359-1365. doi:10.1016/j.neurobiolaging.2007.03.003 | ||
+ | Rife, T., Rasoul, B., Pullen, N., Mitchell, D., Grathwol, K., and Kurth, J. (2009) The effect of a promoter polymorphism on transcription of nitric oxide synthase 1 and its relevance to Parkinson’s disease. Journal of Neuroscience Research. 87, 2319-2325. doi:10.1005/jnr.22045 | ||
<references/> | <references/> |
Revision as of 16:28, 27 April 2016
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References
Shinkai, T., Ohmori, O., Hori, H., and Nakamura, J. (2002) Allelic association of the neuronal nitric oxide synthase (NOS1) gene with schizophrenia. Molecular Psychiatry. 7, 560-563. doi:10.1038/sj.mp.4001041 Galimberti, D., Scarpini, E., Venturelli, E., Strobel, A., Herterich, S., Fenogolio, C., Guidi, I., Scalabrini, D., Cortini, F., Bresolin, N., Lesch, K., and Reif, A. (2008) Association of a NOS1 promoter repeat with Alzheimer’s disease. Neurobiology of Aging. 29, 1359-1365. doi:10.1016/j.neurobiolaging.2007.03.003 Rife, T., Rasoul, B., Pullen, N., Mitchell, D., Grathwol, K., and Kurth, J. (2009) The effect of a promoter polymorphism on transcription of nitric oxide synthase 1 and its relevance to Parkinson’s disease. Journal of Neuroscience Research. 87, 2319-2325. doi:10.1005/jnr.22045
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
- ↑ UniProt Consortium 2009, ‘UniProtKB - P29475 (NOS1_HUMAN),’ UniProtKB Protein Knowledgebase
- ↑ Ward ME, Toporsian M, Scott JA, et al. Hypoxia induces a functionally significant and translationally efficient neuronal NO synthase mRNA variant. Journal of Clinical Investigation. 2005;115(11):3128-3139. doi:10.1172/JCI20806.
- ↑ Juliane Kopf, Martin Schecklmann, Tim Hahn, Thomas Dresler, Alica C. Dieler, Martin J. Herrmann, Andreas J. Fallgatter, Andreas Reif. (2011) NOS1 ex1f-VNTR polymorphism influences prefrontal brain oxygenation during a working memory task, NeuroImage, Volume 57, (Issue 4),1617-1623, Ihttp://dx.doi.org/10.1016/
- ↑ Freudenberg, F., Alttoa, A. & Reif, A. (2015) Neuronal nitric oxide synthase (NOS1) and its adaptor, NOS1AP, as a genetic risk factors for psychiatric. Genes Brain Behav 14, 47–64.
- ↑ Zhang, Y. H., Jin, C. Z., Jang, J. H., & Wang, Y. (2014). Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. The Journal of Physiology, 592(Pt 15), 3189–3200. http://doi.org/10.1113/jphysiol.2013.270306]
- ↑ Zhang, Y. H., Jin, C. Z., Jang, J. H., & Wang, Y. (2014). Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. The Journal of Physiology, 592(Pt 15), 3189–3200. http://doi.org/10.1113/jphysiol.2013.270306]
- ↑ Zhang, Y. H., Jin, C. Z., Jang, J. H., & Wang, Y. (2014). Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. The Journal of Physiology, 592(Pt 15), 3189–3200. http://doi.org/10.1113/jphysiol.2013.270306]