Essential role of Helicobacter pylori apolipoprotein N-acyltransferase (Lnt) in stomach colonization
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE241938 | GEO | 2023/10/17
REPOSITORIES: GEO
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Project description:Essential role of Helicobacter pylori apolipoprotein N-acyltransferase (Lnt) in stomach colonization
| PRJNA1010783 | ENA
Project description:Numerous proteins synthesized in cells ranging from bacteria to humans have to be posttranslationally acylated to become biologically active. Bacterial Repeats in ToXin (RTX) cytolysins form a prominent group of proteins that are synthesized as inactive protoxins and undergo a posttranslational acylation on ε-amino groups of two internal conserved lysine residues by co-expressed toxin-activating acyltransferases. We investigated how the chemical nature, position and number of bound acyl chains govern the activities of Bordetella pertussis adenylate cyclase toxin (CyaA), Escherichia coli α-hemolysin (HlyA) and Kingella kingae cytotoxin (RtxA). The three protoxins were acylated in the same E. coli cell background by either of the CyaC, HlyC and RtxC acyltransferases. The results revealed that the acyltransferase itself selects from the acyl-ACP pool of the producing bacterium the type of the acyl chain of adapted length to be covalently linked to the protoxin. The acyltransferase also selects whether both or only one of two conserved lysine residues of the protoxin will be posttranslationally acylated. Functional assays then revealed that RtxA has to be modified by 14-carbon fatty acyl chains to be biologically active, while HlyA remains active also when modified by 16-carbon acyl chains and CyaA is activated exclusively by 16-carbon acyl chains. These results suggest a structural adaptation of the toxin molecules to the length of the acyl chains used for modification of their crucial acylated lysine residue in the second, more conserved acylation site
2020-05-20 | PXD018859 | Pride
Project description:In zebrafish, maternally deposited yolk is the source of nutrients for embryogenesis prior to digestive system maturation. Yolk nutrients are processed and secreted to the growing organism by an extra-embryonic tissue, the yolk syncytial layer (YSL). Export of lipid from the YSL occurs through the production of triacylglycerol-rich lipoproteins. Here we report that mutations in the triacylglycerol synthesis enzyme, diacylglycerol acyltransferase-2 (Dgat2), cause yolk sac opacity due to aberrant accumulation of cytoplasmic lipid droplets in the YSL. Though triacylglycerol synthesis continues, it is not properly coupled to lipoprotein production as dgat2 mutants produce fewer, smaller, ApoB-containing lipoproteins. Unlike DGAT2-null mice, which are lipopenic and die soon after birth, zebrafish dgat2 mutants are viable, fertile and exhibit normal mass and adiposity. Residual Dgat activity cannot be explained by the activity of other known Dgat isoenzymes, as dgat1a;dgat1b;dgat2 triple mutants continue to produce YSL lipid droplets and remain viable as adults. Further, the newly identified diacylglycerol acyltransferase, Tmem68, is also not responsible for the residual triacylglycerol synthesis activity. Unlike overexpression of Dgat1a and Dgat1b, monoacylglycerol acyltransferase-3 (Mogat3b) overexpression does not rescue yolk opacity, suggesting it does not possess Dgat activity in the YSL. However, mogat3b;dgat2 double mutants exhibit increased yolk opacity and often have structural alterations of the yolk extension. Quadruple mogat3b;dgat1a;dgat1b;dgat2 mutants either have severely reduced viability and stunted growth, or do not survive past 3 days post fertilization, depending on the dgat2 mutant allele present. Our study highlights the remarkable ability of vertebrates to synthesize triacylglycerol through multiple biosynthetic pathways.
2024-11-07 | GSE279170 | GEO
Project description:Ghrelin, an orexigenic gut-derived peptide, is gaining increasing attention due to its multifaceted role in a number of physiological functions, including metabolism, cardiovascular health, stress and reproduction. Ghrelin exists in circulation primarily as des-acylated and acylated ghrelin. Des-acyl ghrelin, until recently considered to be an inactive form ghrelin, is now known to have independent physiological functionality. However, the relative contribution of acyl and des-acyl ghrelin to reproductive development and function is currently unknown. Here we used ghrelin-O-acyltransferase (GOAT) knockout (KO) mice that have no measurable levels of endogenous acyl ghrelin and chronically high levels of des-acyl ghrelin, to characterise how the developmental and life-long absence of acyl ghrelin affects ovarian development and reproductive capacity. We have combined ovarian transcriptome analysis using RNA sequencing with measures of ovarian morphometry, as well as with the assessment of markers of reproductive maturity and the capacity to breed. Our data show pronounced specific changes in the ovarian transcriptome in the juvenile GOAT KO ovary, indicative of advanced ovarian development. These changes corresponded with diminished ovarian reserve in the juvenile and adult ovaries of these mice, due to a continuous reduction in the number of small follicle populations. These changes did not affect the timing of puberty onset or reproductive capacity under optimal conditions. These data suggest that an absence of acyl ghrelin does not prevent reproductive success but that appropriate levels of acyl and des-acyl ghrelin may be necessary for optimal ovarian maturation.
2019-02-05 | GSE106339 | GEO
Project description:The APOE gene is diversified by three alleles e2, e3, and e4 encoding corresponding apolipoprotein (apo) E isoforms. The e4 allele promotes age-related cognitive decline, risk of Alzheimer’s disease (AD), and the rate of AD dementia progression. ApoE is produced by astrocytes as high-density lipoprotein-like particles and these are internalized by neurons upon binding to neuron-expressed apoE receptors. ApoE isoforms differentially engage neuronal plasticity through poorly understood mechanisms. We examined here the effects of native apoE lipoproteins produced by immortalized astrocytes homozygous for e2, e3, and e4 alleles on the maturation and the transcriptomic profile of primary hippocampal neurons. Control neurons were grown in the presence of conditioned media from Apoe-/- astrocytes. ApoE2 and apoE3 significantly increase the dendritic arbor branching, the combined neurite length, and the total arbor surface of the hippocampal neurons, while apoE4 fails to produce similar effects and even significantly reduces the combined neurite length compared to the control. ApoE lipoproteins show no systemic effect on dendritic spine density, yet apoE2 and apoE3 increase the mature spines fraction, while apoE4 increases the immature spine fraction. This is associated with opposing effects of apoE2 or apoE3 and apoE4 on the expression of NR1 NMDA receptor subunit and PSD95. There are 1,062 genes differentially expressed across neurons cultured in the presence of apoE lipoproteins compared to the control. KEGG enrichment and gene ontology analyses show common for apoE2 and apoE3 activation of genes involved in neurite branching, and synaptic signaling. In contrast, apoE4 cultured neurons show upregulation of genes related to the glycolipid metabolism, which are involved in dendritic spine turnover and those which are usually silent in neurons and are related to cell cycle and DNA repair. In conclusion our work reveals that lipoprotein particles comprised of various apoE isoforms differentially regulate neuronal development through interaction with neuronal transcriptome. ApoE4 produces a functionally distinct transcriptomic profile, which is associated with attenuated neuronal development. Differential regulation of neuronal transcriptome by apoE isoforms is a newly identified biological mechanism, which has both implication in the development and aging of the CNS.
2022-05-10 | GSE193162 | GEO
Project description:We have used a lipoprotein-deficient mutant Streptococcus pneumoniae strain, delta lgt, to investigate the role of lipoproteins during inflammatory responses to live S. pneumoniae.
2015-01-31 | E-MTAB-1541 | biostudies-arrayexpress
Project description:To explore how bacterial lipoproteins (i.e. TLR2 ligands) increased macrophage ploidy via mitotic defects, we performed global analysis of cell cycle gene expression changes induced by bacterial lipoproteins. FSL-1 (Pam2CGDPKHPKSF) is a synthetic lipoprotein that represents the N-terminal part of the 44-kDa lipoprotein LP44 of Mycoplasma salivarium. Bone marrow was cultured for 5 days with macrophage colony-stimulating factor (M-CSF), adherent cells were then collected, re-plated and treated either with M-CSF or with M-CSF and FSL-1 for 0, 3, 6 days. The following cell populations were analyzed:<br>-Day 0: After bone marrow culture for 5 days with M-CSF, adherent cells were collected and analyzed.<br>-Day 3, M-CSF: Bone marrow was cultured for 5 days with M-CSF, adherent cells were then collected, re-plated and treated with M-CSF for 3 days. Adherent cells were collected and analyzed.<br>-Day 3, FSL-1: Bone marrow was cultured for 5 days with M-CSF, adherent cells were then collected, re-plated and treated with M-CSF and FSL-1 for 3 days. Adherent cells were collected and analyzed.<br>-Day 6, M-CSF: Bone marrow was cultured for 5 days with M-CSF, adherent cells were then collected, re-plated and treated with M-CSF for 6 days. Adherent cells were collected and analyzed.<br>-Day 6, FSL-1: Bone marrow was cultured for 5 days with M-CSF, adherent cells were then collected, re-plated and treated with M-CSF and FSL-1 for 6 days. Adherent cells, containing polyploid macrophages, were collected and analyzed.
2016-10-27 | E-MTAB-5085 | biostudies-arrayexpress
Project description:ra15-03_oxpmt7-7 - acyltransferase brachypodium-arabidopsis - What biochemical function? What consequence on lignification when overexpressed in Arabidopsis thaliana? - Transcripts of Arabidopsis stem overexpressing an acyl transferase from Brachypodium are compared to wild type plants. The overexpression is under a specific promoter (C4H).
2018-10-01 | GSE120114 | GEO
Project description:We previously found that a native lipoprotein mix with a high VLDL+LDL/HDL ratio causes a global de novoDNA methylation in THP-1 macrophages. In the present experiment we assessed the consequences of global lipoprotein-induced de novo DNA methylation on global gene expression in the same cells. Moreover, we sought to use gene expression array data to measure RNA expression levels for candidate factors mediating the epigenetic effects of lipoproteins. Experiment Overall Design: Human native VLDL, LDL and HDL lipoproteins were isolated from buffy coats, fractionated by ultracentrifugation, stored at -80deg., desalted to PBS before usage and kept at 4deg. for a maximum of 7d. THP-1 monocytes were differentiated to macrophages, stimulated for 24h with a mix of 68.8mg/ml VLDL, 32.1mg/ml LDL, 91.1mg/ml HDL or unstimulated (control), in serum-free medium with 2% BSA. Three independently isolated lipoprotein samples were used in triplicate.
2008-06-16 | E-GEOD-9101 | biostudies-arrayexpress