Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in obesity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA882101 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:There are epidemiological associations between obesity and type 2 diabetes, cardiovascular disease and Alzheimer’s disease. While some common aetiological mechanisms are known, the role of amyloid beta 42 (Ab42) in these diverse chronic diseases is obscure. Here we show that adipose tissue releases Ab42, which is increased from adipose tissue of obese mice and is associated with higher plasma Ab42. Increasing circulating Ab42 levels in mice had no effect on systemic glucose homeostasis but had obesity-like effects on the heart, including reduced cardiac glucose clearance and impaired cardiac function. These effects on cardiac function were not observed when circulating Ab40 levels were increased. Administration of an Ab neutralising antibody prevented obesity-induced cardiac dysfunction and hypertrophy. Furthermore, Ab neutralising antibody administration in established obesity prevented further deterioration of cardiac function. Multi-contrast transcriptomic analyses revealed that Ab42 impacted pathways of mitochondrial metabolism and exposure of cardiomyocytes to Ab42 inhibited mitochondrial function. These data reveal a role for systemic Ab42 in the development of cardiac disease in obesity and suggest that therapeutics designed for Alzheimer’s disease could be effective in combating obesity-induced heart failure.
2022-09-22 | GSE213708 | GEO
Project description:Two carrier-free peptides were synthesized and used in experiments: amyloid beta 42 (DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA), and a scrambled variant with the same chemical constituency as amyloid beta 42 (AIAEGDSHVLKEGAYMEIFDVQGHVFGGKIFRVVDLGSHNVA). To perform blockade current measurements, first, the sub-nanopore was wetted by immersion in de-gassed 250 mM NaCl electrolyte for 1-3 days. Subsequently, to measure the blockade current, a transmembrane voltage bias (< 700 mV) was applied to the reservoir relative to the ground in the channel using Ag/AgCl electrodes and the corresponding pore current was measured using either an Axopatch 700B or an Axopatch 200B amplifier with an open bandwidth. The actual bandwidth was inferred from the rise-time to a sharp (10 ps rise-time) input pulse to be about 75 kHz to 100 kHz, depending on the amplifier and the feedback. The analog data were digitized by a 16-bit DigiData 1550B data acquisition system (DAQ, Molecular Devices, Sunnyvale, CA) at a sampling rate of 500 kS/s and recorded in 3 minute-long acquisition windows. A total of 12 Axon binary files (ABF) were collected for amyloid beta 42, and 71 ABF files for scrambled amyloid beta 42.
2022-06-30 | MSV000089779 | MassIVE
Project description:Whole transcript analysis of amyloid beta 42 (Aβ42)-induced SH-SY5Y cells in control and treated groups (curcumin, piperine and combination therapy) were assessed using microarray profiling. A number of up-regulated and down-regulated genes were altered in sample-specific group. In this study, an optimized concentration of 35 µM of curcumin and piperine in combination was used to treat Aβ42 fibril and then high-throughput microarray profiling (Clariom S assay) was performed on the extracted RNA from pelleted cells.
2020-07-31 | GSE143998 | GEO
Project description:Epidemiological evidence suggests that people chronically exposed to organophosphorus pesticides are at increased risk of neurodegenerative disease. Covalently linked amyloid beta dimers have been isolated from the brains of Alzheimer’s patients. The toxic forms of amyloid beta are amyloid dimers that spontaneously oligomerize. In the present report we treated recombinant and synthetic amyloid beta (1-42) with 1 mM chlorpyrifos oxon or 1 mM paraoxon. The trypsin-digested samples were analyzed by liquid chromatography tandem mass spectrometry on an Orbitrap Fusion Lumos mass spectrometer. Data were searched with Protein Prospector software. We found two new types of crosslinks in amyloid dimers. An isopeptide Asp-Asp link occurred between the N-terminal amine of Asp 1 in one peptide and the beta carboxyl group of Asp 1 in another peptide. An Asp-Arg link occurred between the guanidino group of Arg 5 in one peptide and the beta carboxyl group of Asp 1 in another peptide. These results show that the active metabolites of the pesticides chlorpyrifos and parathion catalyze the crosslinking of amyloid beta (1-42) into toxic dimers. It was concluded that the increased risk of neurodegenerative disease in people exposed to organophosphorus pesticides could be explained by the crosslinking activity of these chemicals.
2022-07-17 | PXD034163 | Pride
Project description:Misfolding and aggregation of proteins is strongly linked to several neurodegenerative diseases, but how such species bring about their cytotoxic actions remains poorly understood. Here we used specifically-designed optical reporter probes and live fluorescence imaging in primary hippocampal neurons to characterise the mechanism by which prefibrillar, oligomeric forms of the Alzheimer's-associated peptide, Aβ42, exert their detrimental effects. We used a pH-sensitive reporter, Aβ42-CypHer, to track Aβ internalisation in real-time, demonstrating that oligomers are rapidly taken up into cells in a dynamin-dependent manner, and trafficked via the endo-lysosomal pathway resulting in accumulation in lysosomes. In contrast, a non-assembling variant of Aβ42 (vAβ42) assayed in the same way is not internalised. Tracking ovalbumin uptake into cells using CypHer or Alexa Fluor tags shows that preincubation with Aβ42 disrupts protein uptake. Our results identify a potential mechanism by which amyloidogenic aggregates impair cellular function through disruption of the endosomal-lysosomal pathway.
| S-EPMC7658065 | biostudies-literature
Project description:Origanum L. (Lamiaceae) is an important genus of medicinal and aromatic plants used in the traditional medicine since ancient times as culinary herbs and remedies. The effects of Origanum majorana-based aromatherapy was investigated in an Alzheimer's amyloid beta1-42 rat model. Protein extracts from brain tissue containing hippocampi were analyzed by label-free quantitative LC-HDMSE. Proteins whose expression seemed influenced by Origanum majorana-based aromatherapy were assigned as representatives of biological processes, which were further targeted using well established biochemical/molecular assays.
2020-09-29 | PXD021082 | Pride
Project description:Heart failure impairs the mechanotransduction properties of human cardiac pericytes
| PRJNA660440 | ENA
Project description:Streptomyces sp. 42 strain:42 Genome sequencing
| PRJNA402572 | ENA
Project description:The goal of this study is to investigate the involvement of inflammation in Alzheimer’s disease (AD) and to clarify the signaling pathways involved in the presence of beta-amyloidosis, a hallmark of AD pathogenesis, to help identifying potential targets for therapy. To do that, we isolated bone marrow-derived progenitor cells from femurs, tibiae and hip bones of non-transgenic C57BL/6 mice according to established protocols , and we maturated them with LPS. To obtain an unbiased view of gene regulation in mouse bone marrow-derived dendritic cells (BM-DCs) exposed to pre-aggregated beta-amyloid peptide (Aβ) oligomers, we analyzed the transcriptome of untreated immature control BM-DCs (‘Ctrl’), LPS-treated BM-DCs (’LPS’), Aβ1-42 oligomer-treated BM-DCs (‘Aβ‘) and BM-DCs treated with Aβ1-42 oligomers and LPS (‘Aβ+LPS‘) via explorative RNA-sequencing.
2019-09-16 | GSE136789 | GEO
Project description:Peripherally-expressed apoE4 impairs brain functions and exacerbates amyloid pathogenesis by compromising cerebrovascular functions
| PRJNA516638 | ENA