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Transcriptome analysis of N1E115 cells cultured in the presence of 20% or 4% O2

ABSTRACT: Neuronal nitric oxide synthase 1 (NOS1) produces the gaseous signaling molecule nitric oxide (NO), which plays important roles in the development and function of the nervous system. The regulation of Nos1 gene expression is incompletely understood. Here, we explored the role of physiological hypoxia in the control of Nos1 transcription and the underlying mechanisms using N1E115 mouse neuroblastoma cells as a model. N1E115 cells were cultured for 3 days at high (20%) and low (4%) oxygen levels. Following the verification of upregulation of Nos1 mRNA and protein levels in response to 4% oxygen, we performed transcriptome analysis using stranded total RNA-sequencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE139472 | GEO | 2024/02/14

REPOSITORIES: GEO

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Project description:This a model from the article: Vascular and perivascular nitric oxide release and transport: biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3). Chen K, Popel AS Free Radic Biol Med. 2007 Mar 15;42(6):811-22. 17320763 , Abstract: Nitric oxide (NO) derived from nitric oxide synthase (NOS) is an important paracrine effector that maintains vascular tone. The release of NO mediated by NOS isozymes under various O(2) conditions critically determines the NO bioavailability in tissues. Because of experimental difficulties, there has been no direct information on how enzymatic NO production and distribution change around arterioles under various oxygen conditions. In this study, we used computational models based on the analysis of biochemical pathways of enzymatic NO synthesis and the availability of NOS isozymes to quantify the NO production by neuronal NOS (NOS1) and endothelial NOS (NOS3). We compared the catalytic activities of NOS1 and NOS3 and their sensitivities to the concentration of substrate O(2). Based on the NO release rates predicted from kinetic models, the geometric distribution of NO sources, and mass balance analysis, we predicted the NO concentration profiles around an arteriole under various O(2) conditions. The results indicated that NOS1-catalyzed NO production was significantly more sensitive to ambient O(2) concentration than that catalyzed by NOS3. Also, the high sensitivity of NOS1 catalytic activity to O(2) was associated with significantly reduced NO production and therefore NO concentrations, upon hypoxia. Moreover, the major source determining the distribution of NO was NOS1, which was abundantly expressed in the nerve fibers and mast cells close to arterioles, rather than NOS3, which was expressed in the endothelium. Finally, the perivascular NO concentration predicted by the models under conditions of normoxia was paradoxically at least an order of magnitude lower than a number of experimental measurements, suggesting a higher abundance of NOS1 or NOS3 and/or the existence of other enzymatic or nonenzymatic sources of NO in the microvasculature. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Chen K, Popel AS (2007) - version02 The original CellML model was created by: Lloyd, Catherine, May c.lloyd@aukland.ac.nz The University of Auckland The Bioengineering Institute This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

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Transcriptome analysis of N1E115 cells cultured in the presence of 20% or 4% O2

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