Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hypoxia-inducible factor cell non-autonomously regulates C. elegans stress responses and behavior via a nuclear receptor

ABSTRACT: The HIF (hypoxia-inducible factor) transcription factor is the master regulator of the metazoan response to chronic hypoxia. In addition to promoting adaptations to low oxygen, HIF drives cytoprotective mechanisms in response to stresses and modulates neural circuit function. How most HIF targets act in the control of the diverse aspects of HIF-regulated biology remains unknown. We discovered that a HIF target, the C. elegans gene cyp-36A1, is required for numerous HIF-dependent processes, including modulation of gene expression, stress resistance, and behavior. cyp-36A1 encodes a cytochrome P450 enzyme that we show controls expression of more than a third of HIF-induced genes. CYP-36A1 acts cell non-autonomously by regulating the activity of the nuclear hormone receptor NHR-46, suggesting that CYP-36A1 functions as a biosynthetic enzyme for a hormone ligand of this receptor. We propose that regulation of HIF effectors through activation of cytochrome P450 enzyme/nuclear receptor signaling pathways could similarly occur in humans.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE108283 | GEO | 2018/07/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

NHR-49 controls a HIF-1 independent hypoxia adaptation pathway in Caenorhabditis elegans

Project description:The response to insufficient oxygen, termed hypoxia, is orchestrated by the conserved master regulator Hypoxia-Inducible Factor-1 (HIF-1), which is hyperactive in many cancers. Here, we describe a HIF-1 independent hypoxia response pathway controlled by Caenorhabditis elegans Nuclear Hormone Receptor NHR-49, an orthologue of mammalian lipid metabolism regulator Peroxisome Proliferator-Activated Receptor alpha (PPARα). nhr-49 is required for worm survival in hypoxia and is synthetically lethal with hif-1 in this context, demonstrating independent activity. RNA-seq data show that nhr-49 regulates a set of hif-1 independent hypoxia responsive genes, including autophagy genes that promote hypoxia survival. We further identified the Nuclear Hormone Receptor nhr-67 as a negative regulator and the Homeodomain-interacting Protein Kinase hpk-1 as a positive regulator in the NHR-49 pathway. Together, our experiments describe an essential hypoxia response pathway controlled by nhr-49 that includes new upstream and downstream components and is as important as hif-1 dependent hypoxia adaptation.

2022-03-16 | GSE166788 | GEO

Transcription profiling of Drosophila Hr39 mutant females reveals the sf1-related nuclear hormone receptor hr39 regulates Drosophila female reproductive tract development and function

Project description:The vertebrate nuclear hormone receptor steroidogenic factor 1 (SF1; NR5A1) controls reproductive development and regulates the transcription of steroid-modifying cytochrome P450 genes. We find that the SF1-related Drosophila nuclear hormone receptor HR39 is also essential for sexual development. In Hr39 mutant females, the sperm-storing spermathecae and glandular parovaria are absent or defective, causing sterility. Our results indicate that spermathecae and parovaria secrete reproductive tract proteins required for sperm maturation and function, like the mammalian epididymis and female reproductive tract. Hr39 controls the expression of specific cytochrome P450 genes and is required in females both to activate spermathecal secretion and repress male-specific courtship genes such as takeout. Thus, a pathway that, in vertebrates, controls sex-specific steroid hormone production, also mediates reproductive functions in an invertebrate. Our findings suggest that Drosophila can be used to model more aspects of mammalian reproductive biology than previously believed. Experiment Overall Design: Wild type and Hr39(04443) Spermathecae, Wild type and Hr39(04443) Reproductive Tract

2008-06-11 | E-GEOD-10264 | biostudies-arrayexpress

Project description:The vertebrate nuclear hormone receptor steroidogenic factor 1 (SF1; NR5A1) controls reproductive development and regulates the transcription of steroid-modifying cytochrome P450 genes. We find that the SF1-related Drosophila nuclear hormone receptor HR39 is also essential for sexual development. In Hr39 mutant females, the sperm-storing spermathecae and glandular parovaria are absent or defective, causing sterility. Our results indicate that spermathecae and parovaria secrete reproductive tract proteins required for sperm maturation and function, like the mammalian epididymis and female reproductive tract. Hr39 controls the expression of specific cytochrome P450 genes and is required in females both to activate spermathecal secretion and repress male-specific courtship genes such as takeout. Thus, a pathway that, in vertebrates, controls sex-specific steroid hormone production, also mediates reproductive functions in an invertebrate. Our findings suggest that Drosophila can be used to model more aspects of mammalian reproductive biology than previously believed. Keywords: mutant/wild-type comparison and tissue comparison

2008-04-26 | GSE10264 | GEO

Effect of Cyp3a-cluster knockout on liver

Project description:Analysis of liver with or without Cytochrome P450 (Cyp) 3a-cluster. Cyp3a family is one of the most important enzymes for drug metabolism. These results suggest the biological effects of Cyp3a-knockout on liver.

2018-11-15 | GSE103533 | GEO

Beta-naphthoflavone treated worms

Project description:The soil nematode Caenorhabditis elegans is one of the simplest animals having the status of a laboratory model. Its genome contains 80 cytochrome P450 genes (CYP). In order to study CYP gene expression in C. elegans mixed stages and synchronized hermaphrodites were exposed to 18 known xenobiotic cytochrome P450 inducers. Messenger RNA expression was detected by DNA arrays and semiquantitative RT-PCR. Using subfamily-specific primers, a pooled set of exon-rich CYP fragments could be amplified. In this way it was possible to systematically check the influence of different inducers on CYP expression at the same time. The well-known CYP1A inducers beta-naphthoflavone, PCB52, and lansoprazol were the most active and in particular they strongly induced almost all CYP35 isoforms. A few number of further CYP forms were found to be inducible by other xenobiotics like phenobarbital, atrazine, and clofibrate. In addition, a transgenic C. elegans line expressing GFP under control of the CYP35A2 promoter showed a strong induction of the fusion by beta-naphthoflavone in the intestine. Copyright 2001 Academic Press. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed

2005-11-25 | E-GEOD-3680 | biostudies-arrayexpress

Effect of Cyp3a-cluster knockout on small intestine

Project description:Analysis of small intestine with or without Cytochrome P450 (Cyp) 3a-cluster. Cyp3a family is one of the most important enzymes for drug metabolism. These results suggest the biological effects of Cyp3a-knockout on small intestine.

2018-11-15 | GSE103534 | GEO

Beta-naphthoflavone treated worms

2005-11-26 | GSE3680 | GEO

mouse liver microsomes phosphorylation

Project description:The microsomes are re-formed vesicle-like artifacts, not ordinarily present in living cells, from pieces of the endoplasmic reticulum (ER), plasma membrane, mitochondria, and Golgi apparatus of broken eukaryotic cells. Typically, microsomes are separated by differential centrifuged from homogenized of cell or tissue. Based on enrichment of ER fractions, prepared microsomes mainly show a large of metabolic activity following high amount of metabolic enzyme, as cytochrome P450 (CYP). CYPs are important components of xenobiotic-metabolizing monooxygenase accounting for an approximate 75% of biotransformation of clinically relevant drugs. Hepatic CYP are ER-anchored hemoproteins involved in the metabolism of numerous endo- and xenobiotics including drugs, steroids, and carcinogens. The CYPs catalytic activity is subject to regulation via phosphorylation. In several previous studies, 8 CYP phosphorylation sites had been discovered in human. Protein kinase A (PKA) and protein kinase C (PKC) were identified as a major catalyst for the phosphorylation of CYPs in 2003. The phosphorylation of CYPs process to their ubiquitination undergoing ubiquitin-dependent 26S proteosomal degradation.

2015-08-24 | PXD002221 | Pride

mouse liver microsomes phosphorylation with LC-MS/MS

2017-04-04 | PXD003043 | Pride