Retinoic acid-induced nNOS expression depends on a novel PI3K/Akt/DAX1 pathway in human TGW-nu-I neuroblastoma cells.
- Authors
- Nagl, Florian; Schönhofer, Katrin; Seidler, Barbara; Mages, Jörg; Allescher, Hans-Dieter; Schmid, Roland M; Schneider, Günter; Saur, Dieter
- Year
- 2009
- Journal
- American journal of physiology. Cell physiology
- PMID
- 19726747
- DOI
- 10.1152/ajpcell.00034.2009
Neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) acts as a neurotransmitter and intracellular signaling molecule in the central and peripheral nervous system. NO regulates multiple processes like neuronal development, plasticity, and differentiation and is a mediator of neurotoxicity. The nNOS gene is highly complex with 12 alternative first exons, exon 1a-1l, transcribed from distinct promoters, leading to nNOS variants with different 5'-untranslated regions. Transcriptional control of the nNOS gene is not understood in detail. To investigate regulation of nNOS gene expression by retinoic acid (RA), we used the human neuroblastoma cell line TGW-nu-I as a model system. We show that RA induces nNOS transcription in a protein synthesis-dependent fashion. We identify the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and the atypical orphan nuclear receptor DAX1 (NR0B1) as critical mediators involved in RA-induced nNOS gene transcription. RA treatment increases DAX1 expression via PI3K/Akt signaling. Upregulation of DAX1 expression in turn induces nNOS transcription in response to RA. These results identify nNOS as a target gene of a novel RA/PI3K/Akt/DAX1-dependent pathway in human neuroblastoma cells and stress the functional importance of the transcriptional regulator DAX1 for nNOS gene expression in response to RA treatment.
No figures extracted from this document.
No chunks — full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
No citations found.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. | 2014 | 25231870 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Retinoic acid alleviates the reduction of Akt and Bad phosphorylation and regulates Bcl-2 family protein interactions in animal models of ischemic stroke. | Kang JB et al. | — | 2024 | → |
| CRYAA and GJA8 promote visual development after whisker tactile deprivation. | Zhang S et al. | — | 2023 | → |
| Sex blind: bridging the gap between drug exposure and sex-related gene expression in <i>Danio rerio</i> using next-generation sequencing (NGS) data and a literature review to find the missing links in pharmaceutical and environmental toxicology studies. | King AC et al. | — | 2023 | → |
| In Vitro Transfection of Up-Regulated Genes Identified in Favorable-Outcome Neuroblastoma into Cell Lines. | Hiyama Y et al. | — | 2022 | → |
| Origin, specification and differentiation of a rare supporting-like lineage in the developing mouse gonad. | Mayère C et al. | — | 2022 | → |
| Somatostatin-Mediated Regulation of Retinoic Acid-Induced Differentiation of SH-SY5Y Cells: Neurotransmitters Phenotype Characterization. | Singh S et al. | — | 2022 | → |
| Inhibition of the antioxidant enzyme PRDX1 activity promotes MPP<sup>+</sup>-induced death in differentiated SH-SY5Y cells and may impair its colocalization with eEF1A2. | Wirakiat W et al. | — | 2020 | → |
| Biocompatible Gold Nanoparticles Ameliorate Retinoic Acid-Induced Cell Death and Induce Differentiation in F9 Teratocarcinoma Stem Cells. | Gurunathan S et al. | — | 2018 | → |
| Cloning, characterization and function analysis of DAX1 in Chinese loach (Paramisgurnus dabryanus). | Xia X et al. | — | 2018 | → |
| Retinoic Acid Antagonizes Testis Development in Mice. | Bowles J et al. | — | 2018 | → |
| The Role of Midkine in Arteriogenesis, Involving Mechanosensing, Endothelial Cell Proliferation, and Vasodilation. | Weckbach LT et al. | — | 2018 | → |
| Structures and regulation of non-X orphan nuclear receptors: A retinoid hypothesis. | Zhi X et al. | — | 2016 | → |
| A Hypothesis for Examining Skeletal Muscle Biopsy-Derived Sarcolemmal nNOSμ as Surrogate for Enteric nNOSα Function. | Chaudhury A | — | 2015 | → |
| Genetic Regulation of Puberty Timing in Humans. | Day FR et al. | — | 2015 | → |
| Intratesticular alpha1-adrenergic receptors mediate stress-disturbed transcription of steroidogenic stimulator NUR77 as well as steroidogenic repressors DAX1 and ARR19 in Leydig cells of adult rats. | Stojkov-Mimic NJ et al. | — | 2015 | → |
| The neurotoxic effects of vitamin A and retinoids. | Oliveira MR | — | 2015 | → |
| Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. | Perry JR et al. | — | 2014 | → |
| PI3K/Akt pathway regulates retinoic acid-induced Hox gene expression in F9 cells. | Lee Y et al. | — | 2014 | → |
| A molecular mechanism of optic nerve regeneration in fish: the retinoid signaling pathway. | Kato S et al. | — | 2013 | → |
| DAX1 regulatory networks unveil conserved and potentially new functions. | Martins RS et al. | — | 2013 | → |
| Diet-induced obesity impairs AKT signalling in the retina and causes retinal degeneration. | Marçal AC et al. | — | 2013 | → |
| Sustained in vivo blockade of α₁-adrenergic receptors prevented some of stress-triggered effects on steroidogenic machinery in Leydig cells. | Stojkov NJ et al. | — | 2013 | → |
| Unexpected neuronal protection of SU5416 against 1-Methyl-4-phenylpyridinium ion-induced toxicity via inhibiting neuronal nitric oxide synthase. | Cui W et al. | — | 2012 | → |
| Midbrain dopaminergic neurons utilize nitric oxide/cyclic GMP signaling to recruit ERK that links retinoic acid receptor stimulation to up-regulation of BDNF. | Kurauchi Y et al. | — | 2011 | → |
| Truncated IRAG variants modulate cGMP-mediated inhibition of human colonic smooth muscle cell contraction. | Werder Av et al. | — | 2011 | → |