Carbon dioxide regulates cholesterol levels through SREBP2
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA804192 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In mammals, O2 and CO2 levels are tightly regulated and are altered under various pathological conditions. While the molecular mechanisms that participate in O2 sensing are well characterized, little is known regarding the signaling pathways that participate in CO2 signaling and adaptation. Here, we show that CO2 levels control a distinct cellular transcriptional response that differs from mere pH changes. Unexpectedly, we discovered that CO2 regulates the expression of cholesterogenic genes in a SREBP2-dependent manner and modulates cellular cholesterol accumulation. Molecular dissection of the underlying mechanism suggests that CO2 triggers SREBP2 activation through changes in endoplasmic reticulum membrane cholesterol levels. Collectively, we propose that SREBP2 participates in CO2 signaling and that cellular cholesterol levels can be modulated by CO2 through SREBP2
2023-10-06 | GSE196294 | GEO
Project description:In mammals, O2 and CO2 levels are tightly regulated and are altered under various pathological conditions. While the molecular mechanisms that participate in O2 sensing are well characterized, little is known regarding the signaling pathways that participate in CO2 signaling and adaptation. Here, we show that CO2 levels control a distinct cellular transcriptional response that differs from mere pH changes. Unexpectedly, we discovered that CO2 regulates the expression of cholesterogenic genes in a SREBP2-dependent manner and modulates cellular cholesterol accumulation. Molecular dissection of the underlying mechanism suggests that CO2 triggers SREBP2 activation through changes in endoplasmic reticulum (ER) membrane cholesterol levels. Collectively, we propose that SREBP2 participates in CO2 signaling and that cellular cholesterol levels can be modulated by CO2 through SREBP2.
| S-EPMC10651039 | biostudies-literature
Project description:Metabolic reprogramming is well-appreciated to be able to control macrophage activation. However, it remains unknown whether the SREBPs-lipogenesis pathway is involved in macrophage alternative (or M2) activation. Here, we showed that IL4-induced M2 activation was coupled with increased SREBP2 maturation and activated cholesterol biosynthetic pathway, while the SREBP1-fatty acid biosynthesis pathway remained unaffected after IL4 stimulation. Genetic or pharmacologic blockade of SREBP2 maturation significantly inhibited IL4-induced M2 activation independent of cholesterol. Instead, cholesterol inhibited M2 activation most likely through its feedback regulation of SREBP2 maturation. Mechanically, the upregulation of SREBP2 maturation was dependent on the activation of upstream MTOR, and mature SREBP2 increased the expression of KAZALD1 and subsequently activated the IGF1 signaling to promote IL4-induced M2 activation. Consistently, myeloid-specific Scap deficiency markedly decreased the number of M2 macrophages in the lung and attenuated the HDM-induced allergic airway inflammation. Taken together, these findings highlight a critical role for cholesterol homeostatic regulator SREBP2 in M2 activation, which advances our understanding of the regulation of immunometabolism for M2 activation and points to new opportunities for therapeutic control of M2 activation and allergic airway inflammation.
2023-04-30 | GSE188356 | GEO
Project description:Macrophage cholesterol homeostasis is crucial for health and disease and has been linked to the lipid-peroxidizing enzyme arachidonate 15-lipoxygenase type B (ALOX15B), albeit molecular mechanisms remain obscure. We performed global transcriptome and immunofluorescence analysis in ALOX15B-silenced primary human macrophages and observed a reduction of nuclear sterol regulatory element-binding protein (SREBP) 2, the master transcription factor of cellular cholesterol biosynthesis. Consequently, SREBP2-target gene expression was reduced as were the sterol biosynthetic intermediates desmosterol and lathosterol as well as 25- and 27-hydroxycholesterol. Mechanistically, suppression of ALOX15B reduced lipid peroxidation in primary human macrophages and thereby attenuated activation of mitogen-activated protein kinase ERK1/2, which lowered SREBP2 abundance and activity. Low nuclear SREBP2 rendered both, ALOX15B-silenced and ERK1/2-inhibited macrophages refractory to SREBP2 activation upon blocking the NPC intracellular cholesterol transporter 1. These studies suggest a regulatory mechanism controlling macrophage cholesterol homeostasis based on ALOX15B-mediated lipid peroxidation and concomitant ERK1/2 activation.
2024-04-07 | GSE208160 | GEO
Project description:Colonoscopy is commonly used in screening for colorectal cancer. A refined technique of colonoscopy involving the use of water as the sole modality to aid colonoscope insertion, water exchange, has been described in recent research papers to decrease patient discomfort and pain, and to reduce the need for sedation during colonoscopy when compared with standard air insufflation. Carbon dioxide insufflation has been described to decrease patient discomfort after colonoscopy. No randomized trial has so far compared the use of water exchange to carbon dioxide insufflation. Our hypothesis is that water exchange inflicts less discomfort to patients undergoing colonoscopy than carbon dioxide insufflation. Patients undergoing screening colonoscopy in two centers in Norway, one center in Poland and one center in The Netherlands will be enrolled and randomized to examination of either of the two methods.
| 2128017 | ecrin-mdr-crc
Project description:The classical bordetellae (Bordetella pertussis, B. parapertussis, and B. bronchiseptica) are obligate aerobes that use only oxygen as their terminal electron acceptor for electron transport-coupled oxidative phosphorylation. Therefore, access to oxygen is critical for these bacteria to survive. To better understand how B. bronchiseptica changes its gene regulation when faced with different levels of oxygen, we grew liquid cultures of B. bronchiseptica RB50 in ambient air, 5% oxygen, and 2% oxygen. We also measured how the presence of 5% carbon dioxide affected gene expression in these bacteria, since they are respiratory pathogens and therefore get exposed to higher carbon dioxide levels during infection than are found in ambient air.
2024-06-07 | GSE268598 | GEO
Project description:There is a growing appreciation that a tight relationship exists between cholesterol homeostasis and immunity in leukocytes, however, this relationship has not been deeply explored in the vascular endothelium. Endothelial cells (ECs) rapidly respond to extrinsic signals, such as tissue damage or microbial infection, by upregulating factors to activate and recruit circulating leukocytes to the site of injury and aberrant activation of ECs leads to inflammatory based diseases, such as multiple sclerosis and atherosclerosis. Here, we studied the role of cholesterol and its master regulator, SREBP2, in the EC responses to inflammatory stress. Treatment of ECs with pro-inflammatory cytokines upregulates SREBP2 cleavage and cholesterol biosynthetic gene expression within the late phase of the acute inflammatory response. Furthermore, SREBP2 activation was dependent on NF-kB DNA binding and canonical SCAP-SREBP2 processing. Mechanistically, inflammatory activation of SREBP was mediated by a reduction in accessible cholesterol, leading to heightened sterol sensing and downstream SREBP2 cleavage. Detailed analysis of NF-kB inducible genes that may impact sterol sensing resulted in the identification of a novel RELA-inducible target, STARD10, that mediates accessible cholesterol homeostasis in ECs. Thus, this study provides an in-depth characterization of the relationship between cholesterol homeostasis and the acute inflammatory response in EC.
2022-04-28 | GSE201466 | GEO
Project description:Comparison of B. bronchiseptica strains RB50 and 761 grown in either atmospheric concentrations of oxygen and carbon dioxide (normal conditions) or in atmospheric levels of oxygen with the addition of 5% carbon dioxide into a sealed incubator (5% CO2 conditions).
2010-10-01 | E-MEXP-2875 | biostudies-arrayexpress
Project description:Plant growth response to elevated levels of CO2 in the environment needs to be deeply investigated to understand the impact of rising global carbon dioxide levels. While the response of plants directly exposed to elevated CO2 is relatively well-studied, the trans-generational impact of elevated CO2 exposure in plants returned to ambient conditions is unexplored. In this study, we show that plants develop a trans-generational memory of elevated CO2 exposure in the next generation even after returning the plants to ambient CO2 levels. By analysing whole genome methylation, we identified that cytosine DNA methylation mechanisms are key to both initiate and maintain this epigenetic memory across generations. Grant ID: EF-1921724 Grant Title: Revealing how epigenetic inheritance governs the environmental challenge response with transformative 3D genomics and machine learning Funding Source: National Science Foundation (NSF)
2023-03-20 | GSE215743 | GEO
Project description:In our work, we uncovered a critical role for cholesterol homeostasis in terminal erythropoiesis. The master transcriptional factor GATA1 binds to Sterol-regulatory element binding protein 2 (SREBP2) to downregulate cholesterol biosynthesis, leading to a gradual reduction in intracellular cholesterol levels. To reveal genetic interactions and epistatic relations between GATA1 and SREBP2 on depth at the whole genome level, we performed RNA sequencing to analyze the gene expression profiles change between treated with Vehicle or β-estradiol in overexpressing active SREBP2 G1E-ER4 cells.
2022-02-08 | GSE184002 | GEO