ABSTRACT: Inhibition of neuronal nitric oxide synthase activity promotes migration of human induced pluripotent stem cell-derived neural stem cells towards cancer cells
Project description: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 analyzed the genome-wide distribution of the histone mark H3K4me3 in FACS-purified nitrergic enteric neurons by chromatin immunoprecipitation-sequencing.
Project description:The dysfunction of endothelial nitric oxide synthase may be involved in development of atherosclerosis; however, the underlying molecular and cellular mechanisms of atherosclerosis are poorly understood. Here, we investigated gene expressionsin relation to atherosclerosis using endothelial nitric oxide synthase (eNOS)-deficient mice.
Project description:The purpose of this study is to comprehensively elucidate the role of nitric oxide and nitric oxide synthase isoforms in pulmonary emphysema using cap analysis of gene expression (CAGE) sequencing.
Project description: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 analyzed 3-dimensional chromosome conformation by HiC.
Project description: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 analyzed HIF1A and ARNT binding by chromatin immunoprecipitation-sequencing.
Project description: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.
Project description:The molecular mechanism underlying the role of hippocampal hilar interneuron degeneration in temporal lobe epilepsy (TLE) remains unclear. Especially, very few studies have focused on the role of neuronal nitric oxide synthase (nNOS, encoded by Nos1) containing hilar interneurons in TLE. In the present study, Nos1 conditional knockout mice were constructed, and we found that selective deletion of Nos1 in hilar interneurons rather than dentate granular cells (DGCs) triggered epileptogenesis. The level of nNOS was downregulated in patients and mice with TLE. Nos1 deletion led to excessive epilepsy-like excitatory input circuit formation and hyperexcitation of DGCs. Replenishment of hilar nNOS protein blocked epileptogenic development and memory impairment in pilocarpine-induced TLE mice. Moreover, chronic treatment with DETA/NONOate, a slowly released exogenous nitric oxide (NO) donor, prevented aberrant neural circuits of DGCs and the consequent epileptogenesis without acute antiseizure effects. Therefore, we concluded that NO donor therapy may be a novel anti-epileptogenesis strategy, different from existing antiseizure medications (ASMs), for curing TLE.
Project description: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 analyzed the genome-wide distribution of the histone marks H3K27ac, H3K27me3, H3K36me3, H3K4me1, and H3K4me3 by chromatin immunoprecipitation-sequencing.
Project description:Tetrahydrobiopterin compounds prolong allograft survival independent of their effect on nitric oxide synthase activity Keywords: other