Changes in gene expression in response to heme deficiency and hypoxia
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ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE9514 | GEO | 2007/11/06
SECONDARY ACCESSION(S): PRJNA103313
REPOSITORIES: GEO
Similar Datasets
Project description:We addressed changes in gene expression profile in response to ; reduced oxygen tension in wild type or heme depletion caused by ; deletion of heme biosynthesis gene hem1 Experiment Overall Design: I.Heme depletion.The hem1 delta strain was grown for 6 hrs in YPD media supplemented with 250 uM ALA. Cells were washed three times with water to remove excess ALA. Cells were then inoculated in duplicates into 15 ml cultures of Experiment Overall Design: YPD media that was supplemented either with or without ALA. Cultures were induced for 16 h before 5 ml of cells were harvested and washed Experiment Overall Design: three times in DEPC water. The culture density at the time of harvest Experiment Overall Design: was approximately OD600=0.5. Experiment Overall Design: II.Hypoxia. BY45742 strain was grown for 6 hrs in Experiment Overall Design: YPD medium and then inoculated in 15 ml the same medium and grown Experiment Overall Design: under normoxic or hypoxic conditions for 12 hrs. To create hypoxic Experiment Overall Design: conditions, cultures were incubated in an anaerobic chamber using a Experiment Overall Design: BBL-GasPak (BD Biosciences).
2008-06-16 | E-GEOD-9514 | biostudies-arrayexpress
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
Project description:Hemes are essential but potentially cytotoxic cofactors that participate in critical and diverse biological processes. Although the pathway and intermediates for heme biosynthesis have been well defined, the intracellular networks which mediate heme trafficking remain unknown. Caenorhabditis elegans and related helminths are natural heme auxotrophs requiring environmental heme for growth and development. We exploited this auxotrophy to identify HRG-1 and HRG-4 in C. elegans and show that they are essential for heme homeostasis and normal vertebrate development. We demonstrate that heme deficiency upregulates expression of hrg-4 and its evolutionarily conserved paralog hrg-1. Depletion of either HRG-1 or HRG-4 in worms results in disruption of organismal heme sensing and abnormal response to heme analogs. HRG-1 and HRG-4 are novel transmembrane proteins that bind heme and have evolutionarily conserved functions. Transient knockdown of hrg-1 in zebrafish leads to hydrocephalus, yolk tube malformations, and, most strikingly, profound defects in erythropoiesis - phenotypes that are fully rescued by worm HRG-1. These findings reveal unanticipated and conserved pathways for cellular heme trafficking in animals that defines the paradigm for eukaryotic heme transport. Uncovering the mechanisms of heme transport in C. elegans will provide novel insights into human disorders of heme metabolism and generate unique anthelmintics to combat worm infestations. Keywords: dose-response
2008-06-13 | GSE8696 | GEO
Project description:Iron plays the central role in the oxygen transport by the erythrocyte as a constituent of heme and hemoglobin. The importance of iron and heme also resides in their regulatory roles during erythroblast maturation. The transcription factor Bach1 may be involved in their regulatory roles since it is inactivated by direct binding of heme. To address whether Bach1 is involved in the responses of erythroblasts to iron status, low iron conditions that induced severe iron deficiency in mice were established. Under iron deficiency, extensive gene expression changes and mitophagy disorder were induced during maturation of erythroblasts. Bach1 mice showed more severe iron deficiency anemia in the developmental phase of mice and a retarded recovery once iron was replenished when compared with wild-type mice. In the absence of Bach1, the expression of globin genes and Hmox1 (encoding heme oxygenase-1) was de-repressed in erythroblasts under iron deficiency, suggesting that Bach1 represses these genes in erythroblasts under iron deficiency to balance the levels of heme and globin. Moreover, an increase in genome-wide DNA methylation was observed in erythroblasts of Bach1–/– mice under iron deficiency. These findings reveal the principle role of iron as a regulator of gene expression in erythroblast maturation and suggest that the iron-heme-Bach1 axis is important for a proper adaptation of erythroblast to iron deficiency to avoid toxic aggregates of non-heme globin.
2016-12-14 | GSE78955 | GEO
Project description:Transcription profiling of P. gingivalis W50 grown in continuous culture under conditions of heme-excess and heme-limitation. Reference design (using Cy5 labelled genomic DNA as the reference) to compare two conditions: heme-excess vs heme-limitation. Three samples for each condition, independently grown.
2010-05-16 | E-GEOD-13375 | biostudies-arrayexpress
Project description:This study compares response to hypoxia in muscle between 2 hypoxia tolerant species of Spalax ehrenbergi, blind subterranean mole rat . The blind subterranean mole rat (Spalax ehrenbergi superspecies) is an excellent model of hypoxic tolerance, living underground and exposed to fluctuating O2 and CO2 levels. Unique structural and functional adaptations of the cardiovascular and respiratory systems allow survival at severely reduced oxygen tension. In this study we have compared expression profiles of muscle tissue between two hypoxia tolerant species of Spalax ehrengergi at normoxic (21%) and hypoxic (3%) levels of oxygen concentration by cross species hybridization using a mouse cDNA array containing 15,000 gene elements. Results uncover numerous genes involved in angiogenesis, apoptosis, and oxidative stress and responding in a species specific manner to hypoxia. Among the most striking, cardiac ankyrin repeat protein (Carp) and activating transcription factor 3 (Atf3), LIM and cysteine-rich domains 1 (Lmcd1) and syndecan 2 (Sdc2). These results support the hypothesis that Spalax is variably adapted to fluctuating oxygen tension. Differences may involve very specific metabolic pathways and functional adaptations at the structural and molecular levels. Elucidation of the natural variation and evolutionary changes under hypoxia within this superspecies may have biomedical applications in ischemic syndromes and cancer. Keywords: hypoxia, Spalax, cDNA microarray
2006-07-14 | GSE3763 | GEO
Project description:Transcription profiling of P. gingivalis W50 grown in continuous culture under conditions of heme-excess and heme-limitation.
2008-11-19 | GSE13375 | GEO
Project description:Sampangine, a plant-derived alkaloid found in the Annonaceae family, exhibits strong inhibitory activity against the opportunistic fungal pathogens Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. In the present study, transcriptional profiling experiments coupled with the analysis of mutants were performed in an effort to elucidate its mechanism of action. Using Saccharomyces cerevisiae as a model organism, we show that sampangine produces a transcriptional response indicative of hypoxia, altering the expression of genes known to respond to low oxygen conditions. Several additional lines of evidence obtained suggest that these responses could involve effects on heme. First, the hem1 deletion mutant lacking the first enzyme in the heme biosynthetic pathway showed increased sensitivity to sampangine, and exogenously supplied hemin partially rescued the inhibitory activity of sampangine in wild-type cells. In addition, heterozygous mutants with deletions in genes involved in five out of eight steps in the heme biosynthetic pathway showed increased susceptibility to sampangine. Furthermore, spectral analysis of pyridine extracts indicated significant accumulation of free porphyrins in sampangine-treated cells. Transcriptional profiling experiments were also performed in C. albicans to investigate the response of a pathogenic fungal species to sampangine. Taking into account the known differences in the physiological responses of C. albicans and S. cerevisiae to low oxygen, significant correlations were observed between the two transcription profiles suggestive of heme-related defects. Our results indicate that the antifungal activity of the plant alkaloid sampangine is due, at least in part, to perturbations in the biosynthesis or metabolism of heme. GSE10073: Gene expression response to the antifungal compound sampangine in S. cerevisiae GSE10075: Gene expression response to the antifungal compound sampangine in C. albicans Keywords: SuperSeries Refer to individual Series
2010-05-26 | E-GEOD-10104 | biostudies-arrayexpress
Project description:Inflammatory macrophage activation is a critical component of the antitumor immune response and an emerging therapeutic concept. To evaluate the impact of heme exposure on antitumoral macrophage activity, we grew spheroids of mixed GFP-MC38 and BMDMs that were either untreated or pretreated with heme, INFγ, or heme + INFγ, and characterized them by scRNA-seq.
2024-01-03 | GSE236996 | GEO
Project description:Transcriptonal profiling of Leuconostoc gasicomitatum LMG18811T (wild type) grown in MRS medium with or without heme. Mutant LMG18811T::pSIP1333A (mutating cydB gene which is essential in the respiratory chain) grown in MRS with or without heme. Comparing mutant and wildtype with and without heme. Two-condition experiments with wild type and cydB mutant. 1) wild type with heme vs wild type without heme (HVV), 2) wild type with heme vs mutant with heme (HMHV) 3) mutant with heme vs mutant without heme (MHM) 4) wildtype without heme vs mutant without heme (MV).
2013-02-08 | E-GEOD-41281 | biostudies-arrayexpress