Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Anti-apoptotic and anti-oxidative effects of DDX24 through HO-1 transcriptional regulation

ABSTRACT: DEAD-box helicase 24 (DDX24) is a member of the DEAD-box protein family, which is essential for various aspects of RNA metabolism. DDX24 has been reported to play a role in ribosome biogenesis, transcription, and mRNA stability. Previous studies have implicated the functions of DDX24 in innate immunity, vascular malformation, cell growth, and cancer progression. Here, we describe a novel function of DDX24 in regulating the oxidative stress response and protecting cells from apoptosis. Our research revealed that DDX24 specifically regulates the expression of the heme oxygenase-1 (HO-1) gene, as determined by RNA sequencing analysis. HO-1 is responsible for degrading heme into carbon monoxide (CO), biliverdin, and ferrous ion (Fe2+), thereby exerting anti-apoptotic and anti-oxidative effects. We validated the regulation of HO-1 by DDX24 in both DDX24-depleted and DDX24-overexpressing HEK293 cells. Our findings indicate that DDX24 is involved in the induction of HO-1 expression under oxidative stress conditions. Importantly, DDX24 regulates the transcription of HO-1 instead of its mRNA stability, likely acting at the promoter and enhancer E1 region of the HO-1 gene. Furthermore, DDX24 depletion in HEK293T cells inhibits cell viability. DDX24 exerts both anti-apoptotic and anti-oxidative effects during oxidative stress. These results suggest that DDX24 plays a crucial role in protecting cells from oxidative stress-induced damage by regulating the transcription of HO-1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE299414 | GEO | 2026/01/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Anti-apoptotic and anti-oxidative effects of DDX24 through HO-1 transcriptional regulation

| PRJNA1274051 | ENA

i.e. RFX8 mediates DDX24 transcription in human hepatocellular carcinoma

Project description:Accumulating evidence suggests that DEAD-box proteins are essential in RNA metabolism and play pivotal roles in cancer progression. However, the mechanisms underlying how DDX24 drives hepatocellular carcinoma (HCC) remain largely unknown. In this study, we demonstrated that DDX24 was an oncogene and identified RFX8 as a DDX24 promoter-binding protein that transcriptionally upregulated DDX24 expression.

2021-01-29 | PXD022650 | Pride

DDX24 promotes hepatocellular carcinoma progression via NCL dependent signaling pathway

Project description:Accumulating evidence suggests that DEAD-box proteins are essential in RNA metabolism and play pivotal roles in cancer progression. However, the mechanisms underlying how DDX24 drives hepatocellular carcinoma (HCC) remain largely unknown. In this study, we demonstrated that DDX24 was an oncogene and identified DDX24 promoted HCC development via interacting with NCL.

2021-01-29 | PXD023321 | Pride

Control of Renal Central Carbon Metabolism by Heme Oxygenase-1

Project description:Metabolic adaptation refers to the regulation of cellular metabolism to prevent tissue dysfunction in response to different forms of stress. Heme, an iron-containing porphyrin, is indispensable for oxygen transport and for the activity of hemoproteins such as catalases. Cytotoxic “labile” heme is readily degraded by two distinct heme oxygenases (HO). The conditional deletion of Hmox-1, the gene encoding the inducible heme-degrading enzyme heme oxygenase (HO)-1, impairs metabolic adaptation to malaria and to polymicrobial infection. Embryonic deficiency in HO-1 is partially lethal in mice and surviving animals show progressive chronic inflammatory disease making them an unsuitable model to study metabolic adaptation. Here we found that mice with an inducible deletion of Hmox1 (Hmox1R26Δ/Δ) but not control mice rapidly succumbed to sterile hemolytic stress. Mortality was associated with heme-driven kidney failure, hypoglycemia, and disruption of adaptive thermoregulation. RNA sequencing and targeted metabolomics combined with data-driven in silico metabolic modeling revealed that failed renal metabolic adaptation is driven by altered oxidative phosphorylation and impaired pentose phosphate pathway. Heme-induced kidney failure and mortality in Hmox1R26Δ/Δ mice was not prevented with impairment of the inflammatory response, nor with antioxidants. Our results emphasize the critical importance of Hmox1 expression in hemolytic stress leading to acute kidney injury and death.

2025-12-02 | GSE246570 | GEO

Co-administration of angiotensin II and simvastatin triggers kidney injury upon heme oxygenase-1 deficiency

Project description:Kidneys are pivotal organ in iron redistribution and can be severely damaged in the course of hemolysis. In our previous studies, we observed that induction of hyper- tension with angiotensin II (Ang II) combined with simvastatin administration results in a high mortality rate or the appearance of signs of kidney failure in heme oxy- genase-1 knockout (HO-1 KO) mice. Here, we aimed to address the mechanisms underlying this effect, focusing on heme and iron metabolism. We show that HO-1 deficiency leads to iron accumulation in the renal cortex. Higher mortality of Ang II and simvastatin-treated HO-1 KO mice coincides with in- creased iron accumulation and the upregulation of mucin-1 in the proximal convoluted tubules. In vitro studies showed that mucin-1 hampers heme- and iron-related oxidative stress through the sialic acid residues. In parallel, knock-down of HO-1 induces the glutathione pathway in an NRF2-depedent manner, which likely protects against heme-induced toxicity. To sum up, we showed that heme degradation during heme overload is not solely dependent on HO-1 enzymatic activity, but can be modulated by the glutathione pathway. We also identified mucin-1 as a novel redox regulator. The results suggest that hypertensive patients with less active HMOX1 alleles may be at higher risk of kidney injury after statin treatment.

2023-06-19 | PXD042995 | Pride

Characterization of R-loop-interacting proteins in embryonic stem cells reveals roles in ribosomal RNA processing and gene expression

Project description:We performed mRNA-seq on mouse embryonic stem cells, with four DEAD-box family proteins, DDX10, DDX24, DDX27, DDX54 being partially depleted using RNA interference. Knockdown of EGFP was carried out as a control. By comparing all four knockdowns, we observed misregulation of a highly-overlapping set of genes, indicating that they regulate mRNA levels through a shared pathway.

2021-08-25 | GSE161890 | GEO

Dual BACH1 regulation by complementary SCF-type E3 ligases

Project description:BACH1, FBXO22, FBXL17, oxidative stress response, E3, Cullin-RING ligases, F-box, cysteine modification, S-nitrosylation, heme

2024-12-03 | PXD051074 | Pride

HO-1 modulates the expression of genes involved in inflammation, angiogenesis, proliferation, apoptosis and cell adhesion in human lung cancer cells.

Project description:The enzymatic activity of HO-1 results in decreased oxidative stress, attenuated inflammatory response, and very often in a lower rate of apoptosis. This is due to removal of heme, a potent prooxidant and proinflammatory agent, but mainly because of generation of biologically active products such as CO and bilirubin. In order to find the correlation between the HO-1 level and the expression of different genes of interest we have utilized human lung cancer cell line NCI-H292 stably overexpressing HO-1. Additionally we have checked if HO-1 can modulate genes expression in NCI-H292 cells treated with TNF. The effect of HO-1 overexpression on transcriptome was assessed by microarray analysis. We have observed that the increase in HO-1 level may affect the expression of different genes involved in cytokine synthesis, angiogenesis, apoptosis, proliferation and cell adhesion. Additionally, HO-1 may interact with the TNF treatment and influence the expression of some genes like IL-1, IL-6, IL-8, FAS and NF-kB.

2011-10-19 | GSE22030 | GEO

Docosahexaenoic acid attenuates metabolic dysfunctions induced by lipopolysaccharide in BV-2 microglial cells

Project description:Microglial cell activation has been linked to many neurodegenerative diseases. Upon stimulation by lipopolysaccharide (LPS), a number of proteins involved in inflammatory and oxidative pathways are activated. Production of nitric oxide has been regarded as a signature marker of inflammatory responses. Our recent studies demonstrated the effects of docosahexaenoic acid (DHA) to inhibit the LPS-induced inflammatory responses in BV-2 microglial cells. DHA also can upregulate the anti-oxidative pathway involving nuclear factor erythroid 2-Like 2 (Nrf2) and synthesis of heme oxygenase-1 (HO-1), a potent anti-oxidative enzyme. In order to further understand the proteins involved, this study used a label-free quantitative proteomics approach to examine effects of DHA and LPS on proteins and signaling pathways in microglial cells.

2020-04-20 | PXD013086 | Pride

HO-1 modulates the expression of genes involved in inflammation, angiogenesis, proliferation, apoptosis and cell adhesion in human lung cancer cells.

2011-10-18 | E-GEOD-22030 | biostudies-arrayexpress