ArticleBMC genomics2005
cGMP-independent nitric oxide signaling and regulation of the cell cycle.
Article in BMC genomics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
16 citing papers in PubMed, 51 citations in OpenAlex.
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- The Role of Gasotransmitter-Dependent Signaling Mechanisms in Apoptotic Cell Death in Cardiovascular, Rheumatic, Kidney, and Neurodegenerative Diseases and Mental Disorders.International journal of molecular sciences · 2023Review
- NO-Dependent Mechanisms of p53 Expression and Cell Death in Rat's Dorsal Root Ganglia after Sciatic-Nerve Transection.Biomedicines · 2022Article
- Antinociceptive Activity of Methanolic Extract ofPain research & management · 2018Article
- The role of nitric oxide during embryonic epidermis development ofBiology open · 2017Article
- Nitric Oxide Has a Concentration-Dependent Effect on the Cell Cycle ActingFrontiers in physiology · 2017Article
- Reduction of nitric oxide level leads to spontaneous resumption of meiosis in diplotene-arrested rat oocytes cultured in vitro.Experimental biology and medicine (Maywood, N.J.) · 2015Article
- Characterization of antioxidant and anti-inflammatory activities of bioactive fractions recovered from a glucose-lysine Maillard reaction model system.Molecular and cellular biochemistry · 2012Article
- Transport rather than diffusion-dependent route for nitric oxide gas activity in alveolar epithelium.Free radical biology & medicine · 2010Article
- Nitric oxide and cancer therapy: the emperor has NO clothes.Current pharmaceutical design · 2010Review
- Nitric oxide as a signaling molecule in the fission yeast Schizosaccharomyces pombe.Protoplasma · 2009Article
- Inhaled ethyl nitrite prevents hyperoxia-impaired postnatal alveolar development in newborn rats.American journal of respiratory and critical care medicine · 2007Article
- Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements.Nucleic acids research · 2006Article
- Neuronal nitric oxide synthase contributes to the regulation of hematopoiesis.Molecular medicine (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundRegulatory functions of nitric oxide (NO*) that bypass the second messenger cGMP are incompletely understood. Here, cGMP-independent effects of NO* on gene expression were globally examined in U937 cells, a human monoblastoid line that constitutively lacks soluble guanylate cyclase. Differentiated U937 cells (>80% in G0/G1) were exposed to S-nitrosoglutathione, a NO* donor, or glutathione alone (control) for 6 h without or with dibutyryl-cAMP (Bt2cAMP), and then harvested to extract total RNA for microarray analysis. Bt2cAMP was used to block signaling attributable to NO*-induced decreases in cAMP.
resultsNO* regulated 110 transcripts that annotated disproportionately to the cell cycle and cell proliferation (47/110, 43%) and more frequently than expected contained AU-rich, post-transcriptional regulatory elements (ARE). Bt2cAMP regulated 106 genes; cell cycle gene enrichment did not reach significance. Like NO*, Bt2cAMP was associated with ARE-containing transcripts. A comparison of NO* and Bt2cAMP effects showed that NO* regulation of cell cycle genes was independent of its ability to interfere with cAMP signaling. Cell cycle genes induced by NO* annotated to G1/S (7/8) and included E2F1 and p21/Waf1/Cip1; 6 of these 7 were E2F target genes involved in G1/S transition. Repressed genes were G2/M associated (24/27); 8 of 27 were known targets of p21. E2F1 mRNA and protein were increased by NO*, as was E2F1 binding to E2F promoter elements. NO* activated p38 MAPK, stabilizing p21 mRNA (an ARE-containing transcript) and increasing p21 protein; this increased protein binding to CDE/CHR promoter sites of p21 target genes, repressing key G2/M phase genes, and increasing the proportion of cells in G2/M.
conclusionNO* coordinates a highly integrated program of cell cycle arrest that regulates a large number of genes, but does not require signaling through cGMP. In humans, antiproliferative effects of NO* may rely substantially on cGMP-independent mechanisms. Stress kinase signaling and alterations in mRNA stability appear to be major pathways by which NO* regulates the transcriptome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.