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Project description: Not available
| S-EPMC5878102 | biostudies-literature
Project description:Revisiting the putative role of heme as a trigger of inflammation
| PRJNA395535 | ENA
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:Heme, an iron-containing tetrapyrrole, serves physiological functions as a prosthetic group of various hemoproteins. By contrast, excess free heme that is not bound to proteins can be harmful via its pro-oxidant and cytotoxic effects. In macrophages, heme appears to induce both- pro- and anti-inflammatory activation but the underlying mechanisms are not well understood. Here, we compared the response of human blood-monocyte derived macrophages (hMDMs) and mouse bone-marrow derived macrophages (mBMDMs) to heme and the Toll-like receptor (TLR)4 ligand lipopolysaccharide (LPS), particularly focusing on how energetic metabolism is modulated in these two cell types. We found that, in contrast to LPS, heme led to an anti-inflammatory transcriptional profile in hMDMs, as demonstrated by bulk RNA-sequencing. Moreover, heme and LPS caused distinct regulatory patterns of inflammatory activation and cellular bioenergetics in hMDMs and mBMDMs. Specifically, in LPS-stimulated mBMDMs, but not in hMDMs, heme caused a marked suppression of oxidative phosphorylation and an up-regulation of glycolysis. The differential responses to heme in macrophages were determined by the availability of nitric oxide (NO) that is generated in activated mBMDMs, but not in inflammatory hMDMs. Taken together, the current findings indicate that alterations of mitochondrial metabolism and glycolysis play a critical role for determining specific immunomodulatory effects of heme in inflammatory human and mouse macrophages.
2024-05-13 | GSE255234 | GEO
Project description:The response regulator HrrA belonging to the HrrSA two-component system (previously named CgtSR11) is known to be repressed by the global iron-dependent regulator DtxR in Corynebacterium glutamicum. Sequence analysis indicated an involvement of the HrrSA system in heme-dependent gene expression. Growth experiments revealed that the non-pathogenic soil bacterium C. glutamicum is able to use hemin or hemoglobin as sole iron source. In DNA microarray analyses a putative operon encoding the hemin-binding protein HtaA and the putative hemin ABC transporter HmuTUV showed a strong upregulation in heme-grown cells. Deletion of the hmu operon clearly affects heme utilization, but does not completely abolish growth on heme or hemoglobin. As a central part of this study, we investigated the regulon of the response regulator HrrA via comparative transcriptome analysis of a hrrA deletion mutant and C. glutamicum wild type in combination with DNA-protein interaction studies with purified HrrA protein. Our data provide evidence for a heme-dependent transcriptional activation of heme oxygenase (hmuO), an enzyme involved in the utilization of heme as iron source. Besides hmuO, HrrA was shown to activate the expression of heme-containing components of the respiratory chain, namely ctaD and the ctaE-qcrCAB operon encoding subunits I and III of cytochrome aa3 oxidase and three subunits of the cytochrome bc1 complex. Furthermore, HrrA represses almost all genes involved in heme biosynthesis, including glutamyl-tRNA reductase (hemA), uroporphyrinogen decarboxylase (hemE), and ferrochelatase (hemH). Thus, our data clearly emphasize a central role of the HrrSA system in the control of heme homeostasis in C. glutamicum. Three biological replicates of each experiment were performed. Experiment 1: Transcriptome comparison of wild type grown und FeSO4 or heme as iron source; Exp. 2: WT vs. hrrA deletion mutant grown on FeSO4; Exp. 3: WT vs. hrrA mutant grown on heme. For analysis via DNA microarraysose RNA was isolated from exponentially growing cells cultivated in CgXII medium containing glucose as carbon source and either 2.5 uM FeSO4 or 2.5 uM heme as iron source.
2010-12-17 | E-GEOD-26122 | biostudies-arrayexpress
Project description:The response regulator HrrA belonging to the HrrSA two-component system (previously named CgtSR11) is known to be repressed by the global iron-dependent regulator DtxR in Corynebacterium glutamicum. Sequence analysis indicated an involvement of the HrrSA system in heme-dependent gene expression. Growth experiments revealed that the non-pathogenic soil bacterium C. glutamicum is able to use hemin or hemoglobin as sole iron source. In DNA microarray analyses a putative operon encoding the hemin-binding protein HtaA and the putative hemin ABC transporter HmuTUV showed a strong upregulation in heme-grown cells. Deletion of the hmu operon clearly affects heme utilization, but does not completely abolish growth on heme or hemoglobin. As a central part of this study, we investigated the regulon of the response regulator HrrA via comparative transcriptome analysis of a hrrA deletion mutant and C. glutamicum wild type in combination with DNA-protein interaction studies with purified HrrA protein. Our data provide evidence for a heme-dependent transcriptional activation of heme oxygenase (hmuO), an enzyme involved in the utilization of heme as iron source. Besides hmuO, HrrA was shown to activate the expression of heme-containing components of the respiratory chain, namely ctaD and the ctaE-qcrCAB operon encoding subunits I and III of cytochrome aa3 oxidase and three subunits of the cytochrome bc1 complex. Furthermore, HrrA represses almost all genes involved in heme biosynthesis, including glutamyl-tRNA reductase (hemA), uroporphyrinogen decarboxylase (hemE), and ferrochelatase (hemH). Thus, our data clearly emphasize a central role of the HrrSA system in the control of heme homeostasis in C. glutamicum.
2010-12-17 | GSE26122 | GEO
Project description:Porphyromonas gingivalis is an anaerobic, Gram-negative oral pathogen associated with chronic periodontitis. P. gingivalis has an obligate requirement for heme which it obtains from the host. Heme availability has been linked to disease initiation and progression. In this study we used continuous culture of the bacterium to determine the effect of heme limitation and excess on the P. gingivalis proteome. Four biological replicates of whole cell lysate (WCL) and outer membrane vesicle (OMV) samples were digested with trypsin and analysed by tandem mass spectrometry and MaxQuant label-free quantification. In total, 1211 proteins were quantified with 108 and 49 proteins significantly changing in abundance more than 1.5-fold (p<0.05) in the WCLs and OMVs respectively. The proteins most upregulated in response to heme limitation were those involved in binding and transporting heme while the four proteins most upregulated in the heme excess condition constitute a putative heme efflux system. In general, the protein abundance ratios obtained for OMVs and WCLs agreed, indicating that changes to the OM protein composition are passed on to OMVs, however 16 proteins were preferentially packaged into OMVs in one condition more than the other. In particular, moonlighting cytoplasmic proteins were preferentially associated with OMVs under heme excess.
2018-05-18 | PXD009730 | Pride
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:We recently showed that the two-component system (TCS) HrrSA plays a central role in the control of heme homeostasis in the Gram-positive soil bacterium Corynebacterium glutamicum. Here, we characterized the function of another TCS of this organism, ChrSA, which exhibits significant sequence similarity to HrrSA, and provide evidence for cross-regulation of the two systems. In this study ChrSA was shown to be crucial for heme resistance of C. glutamicum by activation of the putative heme-detoxifying ABC-transporter HrtBA in the presence of heme. Deletion of either hrtBA or chrSA resulted in a strongly increased sensitivity towards heme. DNA microarray analysis and gel retardation assays with the purified response regulator ChrA provided evidence for ChrA being a repressor of the heme biosynthesis operon hemAC and hemH and an activator of the ctaE-qcrCAB operon, encoding subunits of the cytochrome bc1-aa3 supercomplex of the respiratory chain. The heme oxygenase gene, hmuO, showed a strongly decreased mRNA level in the M-NM-^TchrSA mutant, but no significant binding of ChrA was observed in vitro. Promoter fusion studies of PchrSA with eyfp indicated positive autoregulation of the chrSA operon in the presence of heme. Interestingly, ChrA was also shown to bind to the hrrA promoter and to repress transcription of the paralog response regulator, suggesting a close link between HrrSA and ChrSA. Mutational analysis and in silico prediction resulted in the deduction of a 16-bp weakly conserved inverted repeat as consensus DNA-binding motif of ChrA. Altogether, the present study emphasizes ChrSA as a second TCS, besides HrrSA, involved in heme-dependent gene regulation in C. glutamicum. To identify the influence of ChrSA on global gene expression , DNA microarray analyses were performed with the M-NM-^TchrSA mutant compared to C. glutamicum wild type. For this purpose RNA was isolated from exponentially growing cells cultivated in CgXII minimal medium with 4% glucose and either 2.5 M-BM-5M FeSO4 or 2.5 M-BM-5M hemin as iron source. Three biological replicates were performed.
2012-10-31 | E-GEOD-37327 | biostudies-arrayexpress
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