Beta-hydroxybutyrate is a metabolic regulator of proteostasis in aging and Alzheimer disease
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Exploris 480
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Birgit Schilling
PROVIDER: MSV000091514 | MassIVE | Mon Mar 20 16:34:00 GMT 2023
SECONDARY ACCESSION(S): PXD040985
REPOSITORIES: MassIVE
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Project description:Aging proteins in the lens become increasingly aggregated and insoluble, contributing to presbyopia. In this study, we investigated the ability of aggrelyte-2 (N,S-Diacetyl-L-cysteine methyl ester) to reverse the water insolubility of aged human lens proteins and to decrease stiffness in cultured human and rodent lenses. Aggrelyte-2 was incubated (500 µM) with water-insoluble proteins of aged human lenses (65-75 years) for 24 or 48 h. A control compound that lacked an S-acetyl group (aggrelyte-2C) was also tested. We observed 19-30% solubility of WI upon the treatment with aggrelyte-2. Aggrelyte-2C also increased protein solubility, but its effect was approximately 1.4-fold lower than that of aggrelyte-2. The protein thiol contents were 1.9 to 4.9-fold higher in the aggrelyte-treated samples than in the untreated samples. The LC-MS/MS results showed N-acetyllysine (AcK) levels of 1.5 to 2.1 nmoles/mg protein and 0.6 to 0.9 nmoles/mg protein in the aggrelyte-2- and aggrelyte-2C-treated samples, respectively. Mouse (C57BL/6J) lenses (incubated for 24 h) and human lenses (incubated for 72 h) with 1.0 mM aggrelyte-2 showed significant decreases in stiffness with simultaneous increases in soluble proteins (human lenses) and protein-AcK levels and such changes were not observed in aggrelyte-2C treated lenses. Mass spectrometry of the solubilized protein revealed AcK in all crystallins but more in α-crystallins. These results suggest that aggrelyte-2 increases protein solubility and decreases lens stiffness through acetylation and disulfide reduction. Aggrelyte-2 might be useful in treating presbyopia in humans.
2023-05-10 | PXD035049 | Pride
Project description:We applied genome-wide profiling to successive salt-extracted fractions of micrococcal nuclease-treated Drosophila chromatin. Chromatin fractions extracted with 80mM or 150mM NaCl after digestion contain predominantly mononucleosomes and represent calssical 'active' chromatin. Profiles of these low-salt-soluble fractions display phased nucleosomes over transcriptionally active genes that are locally depleted of histone H3.3 and correspond closely to profiles of RNA polymerase II. Nearly quantitative recovery of chromatin is obtained with 600mM NaCl, however, the remaining insoluble chromatin is enriched in actively transcribed regions. Salt-insoluble chromatin likely represents oligonucleosomes that are attached to large protein complexes. Both low-salt extracted and insoluble chromatin are rich in sequences that correspond to epigenetic regulatory elements genome-wide. The presence of active chromatin at both extremes of salt solubility suggests that these salt fractions capture bound and unbound intermediates in active processes, thus providing a simple, powerful strategy for mapping epigenome dynamics. Keywords: Chromatin affinity-purification on microarray For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf All experiments were done using two channels per chip, comparing DNAs extracted from either salt-extracted or insoluble chromatin to whole nuclear chromatin, whole nuclear chromatin to randomly fragmented genomic DNA, streptavidin-bound biotin-tagged histone-variant-containing chromatin to salt-extracted chromatin, gel-purified mononucleosomes to whole EDTA-extracted soluble chromatin, streptavidin-bound biotin-tagged histone-variant-containing chromatin to whole EDTA-extracted soluble chromatin, or oligo(dT)-primed cDNA to randomly fragmented genomic DNA from S2 cell nuclei.
2008-12-11 | E-GEOD-13217 | biostudies-arrayexpress
Project description:modENCODE_submission_2756 This submission comes from a modENCODE project of Steven Henikoff. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We applied genome-wide profiling to successive salt-extracted fractions of micrococcal nuclease-treated Drosophila chromatin. Chromatin fractions extracted with 80 mM or 150 mM NaCl after digestion contain predominantly mononucleosomes and represent classical "active" chromatin. Profiles of these low-salt soluble fractions display phased nucleosomes over transcriptionally active genes that are locally depleted of histone H3.3 and correspond closely to profiles of histone H2Av (H2A.Z) and RNA polymerase II. This correspondence suggests that transcription can result in loss of H3.3+H2Av nucleosomes and generate low-salt soluble nucleosomes. Nearly quantitative recovery of chromatin is obtained with 600 mM NaCl; however, the remaining insoluble chromatin is enriched in actively transcribed regions. Salt-insoluble chromatin likely represents oligonucleosomes that are attached to large protein complexes. Both low-salt extracted and insoluble chromatin are rich in sequences that correspond to epigenetic regulatory elements genome-wide. The presence of active chromatin at both extremes of salt solubility suggests that these salt fractions capture bound and For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: tiling array analysis. BIOLOGICAL SOURCE: Cell Line: Kc167; Tissue: embryo-derived cell-line; Developmental Stage: late embryonic stage; Genotype: se/e; Sex: Female; NUMBER OF REPLICATES: 2; EXPERIMENTAL FACTORS: Cell Line Kc167; biochemical fraction (extract) soluble fraction; sodium chloride concentration (Compound) 600 mM; extraction time (sampling_time_point) 1 to 2 hours
2010-11-18 | E-GEOD-25385 | biostudies-arrayexpress
Project description:modENCODE_submission_2759 This submission comes from a modENCODE project of Steven Henikoff. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We applied genome-wide profiling to successive salt-extracted fractions of micrococcal nuclease-treated Drosophila chromatin. Chromatin fractions extracted with 80 mM or 150 mM NaCl after digestion contain predominantly mononucleosomes and represent classical "active" chromatin. Profiles of these low-salt soluble fractions display phased nucleosomes over transcriptionally active genes that are locally depleted of histone H3.3 and correspond closely to profiles of histone H2Av (H2A.Z) and RNA polymerase II. This correspondence suggests that transcription can result in loss of H3.3+H2Av nucleosomes and generate low-salt soluble nucleosomes. Nearly quantitative recovery of chromatin is obtained with 600 mM NaCl; however, the remaining insoluble chromatin is enriched in actively transcribed regions. Salt-insoluble chromatin likely represents oligonucleosomes that are attached to large protein complexes. Both low-salt extracted and insoluble chromatin are rich in sequences that correspond to epigenetic regulatory elements genome-wide. The presence of active chromatin at both extremes of salt solubility suggests that these salt fractions capture bound and unbound intermediates in active processes, thus providing a simple, powerful strategy for mapping epigenome dynamics. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: tiling array analysis. BIOLOGICAL SOURCE: Cell Line: Kc167; Tissue: embryo-derived cell-line; Developmental Stage: late embryonic stage; Genotype: se/e; Sex: Female; NUMBER OF REPLICATES: 2; EXPERIMENTAL FACTORS: Cell Line Kc167; biochemical fraction (extract) soluble fraction; sodium chloride concentration (Compound) 600 mM; extraction time (sampling_time_point) 1 to 2 hours
2010-11-18 | E-GEOD-25388 | biostudies-arrayexpress
Project description:modENCODE_submission_2513 This submission comes from a modENCODE project of Steven Henikoff. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We applied genome-wide profiling to successive salt-extracted fractions of micrococcal nuclease-treated Drosophila chromatin. Chromatin fractions extracted with 80 mM or 150 mM NaCl after digestion contain predominantly mononucleosomes and represent classical "active" chromatin. Profiles of these low-salt soluble fractions display phased nucleosomes over transcriptionally active genes that are locally depleted of histone H3.3 and correspond closely to profiles of histone H2Av (H2A.Z) and RNA polymerase II. This correspondence suggests that transcription can result in loss of H3.3+H2Av nucleosomes and generate low-salt soluble nucleosomes. Nearly quantitative recovery of chromatin is obtained with 600 mM NaCl; however, the remaining insoluble chromatin is enriched in actively transcribed regions. Salt-insoluble chromatin likely represents oligonucleosomes that are attached to large protein complexes. Both low-salt extracted and insoluble chromatin are rich in sequences that correspond to epigenetic regulatory elements genome-wide. The presence of active chromatin at both extremes of salt solubility suggests that these salt fractions capture bound and For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: tiling array analysis. BIOLOGICAL SOURCE: Cell Line: ML-DmD16-c3; Tissue: dorsal mesothoracic disc; Developmental Stage: third instar larval stage; Genotype: y v f mal; Sex: Female; NUMBER OF REPLICATES: 2; EXPERIMENTAL FACTORS: Cell Line ML-DmD16-c3; biochemical fraction (extract) soluble fraction; sodium chloride concentration (Compound) 80 mM; extraction time (sampling_time_point) 1-2 hours
2010-11-18 | E-GEOD-25381 | biostudies-arrayexpress
Project description:modENCODE_submission_2514 This submission comes from a modENCODE project of Steven Henikoff. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We applied genome-wide profiling to successive salt-extracted fractions of micrococcal nuclease-treated Drosophila chromatin. Chromatin fractions extracted with 80 mM or 150 mM NaCl after digestion contain predominantly mononucleosomes and represent classical "active" chromatin. Profiles of these low-salt soluble fractions display phased nucleosomes over transcriptionally active genes that are locally depleted of histone H3.3 and correspond closely to profiles of histone H2Av (H2A.Z) and RNA polymerase II. This correspondence suggests that transcription can result in loss of H3.3+H2Av nucleosomes and generate low-salt soluble nucleosomes. Nearly quantitative recovery of chromatin is obtained with 600 mM NaCl; however, the remaining insoluble chromatin is enriched in actively transcribed regions. Salt-insoluble chromatin likely represents oligonucleosomes that are attached to large protein complexes. Both low-salt extracted and insoluble chromatin are rich in sequences that correspond to epigenetic regulatory elements genome-wide. The presence of active chromatin at both extremes of salt solubility suggests that these salt fractions capture bound and For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: tiling array analysis. BIOLOGICAL SOURCE: Cell Line: ML-DmD16-c3; Tissue: dorsal mesothoracic disc; Developmental Stage: third instar larval stage; Genotype: y v f mal; Sex: Female; NUMBER OF REPLICATES: 2; EXPERIMENTAL FACTORS: Cell Line ML-DmD16-c3; biochemical fraction (extract) soluble fraction; sodium chloride concentration (Compound) 150 mM; extraction time (sampling_time_point) 1-2 hours
2010-11-18 | E-GEOD-25382 | biostudies-arrayexpress
Project description:modENCODE_submission_2515 This submission comes from a modENCODE project of Steven Henikoff. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We applied genome-wide profiling to successive salt-extracted fractions of micrococcal nuclease-treated Drosophila chromatin. Chromatin fractions extracted with 80 mM or 150 mM NaCl after digestion contain predominantly mononucleosomes and represent classical "active" chromatin. Profiles of these low-salt soluble fractions display phased nucleosomes over transcriptionally active genes that are locally depleted of histone H3.3 and correspond closely to profiles of histone H2Av (H2A.Z) and RNA polymerase II. This correspondence suggests that transcription can result in loss of H3.3+H2Av nucleosomes and generate low-salt soluble nucleosomes. Nearly quantitative recovery of chromatin is obtained with 600 mM NaCl; however, the remaining insoluble chromatin is enriched in actively transcribed regions. Salt-insoluble chromatin likely represents oligonucleosomes that are attached to large protein complexes. Both low-salt extracted and insoluble chromatin are rich in sequences that correspond to epigenetic regulatory elements genome-wide. The presence of active chromatin at both extremes of salt solubility suggests that these salt fractions capture bound and For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: tiling array analysis. BIOLOGICAL SOURCE: Cell Line: ML-DmD16-c3; Tissue: dorsal mesothoracic disc; Developmental Stage: third instar larval stage; Genotype: y v f mal; Sex: Female; NUMBER OF REPLICATES: 2; EXPERIMENTAL FACTORS: Cell Line ML-DmD16-c3; biochemical fraction (extract) soluble fraction; sodium chloride concentration (Compound) 600 mM; extraction time (sampling_time_point) 1-2 hours
2010-11-18 | E-GEOD-25383 | biostudies-arrayexpress
Project description:Amyloid-beta (Aβ) plays a key role in the pathogenesis of Alzheimer’s disease (AD), but little is known about the proteoforms present in human AD brain. We used high-resolution mass spectrometry to analyze intact, undigested Aβ from purified soluble aggregates and insoluble material in brains of 6 cases with severe dementia and pathologically confirmed AD. The soluble aggregates are especially relevant because they are believed to be the most toxic form of Aβ. We found a diversity of Aβ peptides, with 26 unique proteoforms including various N- and C-terminal truncations. N- and C-terminal truncations comprised 73% and 30%, respectively, of the number of Aβ proteoforms detected. The Aβ proteoforms segregated between the soluble and more insoluble aggregates with N-terminal truncations predominating in the insoluble material and C- terminal truncations segregating into the soluble aggregates. In contrast, canonical Aβ comprised the minority of the number of identified proteoforms (15.3%) and did not distinguish between the soluble and more insoluble aggregates. The relative abundance of many truncated Aβ proteoforms did not correlate with post-mortem interval, suggesting they are not artefacts. This heterogeneity of Aβ proteoforms deepens our understanding of AD and offers many new avenues for investigation into pathological mechanisms of the disease, with implications for therapeutic development.
2017-08-28 | PXD006552 | Pride
Project description:modENCODE_submission_2511 This submission comes from a modENCODE project of Steven Henikoff. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We applied genome-wide profiling to successive salt-extracted fractions of micrococcal nuclease-treated Drosophila chromatin. Chromatin fractions extracted with 80 mM or 150 mM NaCl after digestion contain predominantly mononucleosomes and represent classical "active" chromatin. Profiles of these low-salt soluble fractions display phased nucleosomes over transcriptionally active genes that are locally depleted of histone H3.3 and correspond closely to profiles of histone H2Av (H2A.Z) and RNA polymerase II. This correspondence suggests that transcription can result in loss of H3.3+H2Av nucleosomes and generate low-salt soluble nucleosomes. Nearly quantitative recovery of chromatin is obtained with 600 mM NaCl; however, the remaining insoluble chromatin is enriched in actively transcribed regions. Salt-insoluble chromatin likely represents oligonucleosomes that are attached to large protein complexes. Both low-salt extracted and insoluble chromatin are rich in sequences that correspond to epigenetic regulatory elements genome-wide. The presence of active chromatin at both extremes of salt solubility suggests that these salt fractions capture bound and For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: tiling array analysis. BIOLOGICAL SOURCE: Strain: B3(made_by : Paul Talbert description : A strain that expresses a conditionally expressed biotin-tagged histone H3.3. The strain also contains the E. coli BirA gene that is expressed under the control of a GAL4 UAS. tags : Transposon transgene : Histone H3.3::biotin-recognition-peptide outcross : New Line genotype : y w; A5C-GAL4/cyO; B3 official name : B3 ); Genotype: y w; A5C-GAL4/cyO; B3; Transgene: Histone H3.3::biotin-recognition-peptide; NUMBER OF REPLICATES: 2; EXPERIMENTAL FACTORS: biochemical fraction (extract) soluble fraction; sodium chloride concentration (Compound) 600 mM; extraction time (sampling_time_point) 1-2 hours
2010-11-18 | E-GEOD-25379 | biostudies-arrayexpress
Project description:modENCODE_submission_2760 This submission comes from a modENCODE project of Steven Henikoff. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We applied genome-wide profiling to successive salt-extracted fractions of micrococcal nuclease-treated Drosophila chromatin. Chromatin fractions extracted with 80 mM or 150 mM NaCl after digestion contain predominantly mononucleosomes and represent classical "active" chromatin. Profiles of these low-salt soluble fractions display phased nucleosomes over transcriptionally active genes that are locally depleted of histone H3.3 and correspond closely to profiles of histone H2Av (H2A.Z) and RNA polymerase II. This correspondence suggests that transcription can result in loss of H3.3+H2Av nucleosomes and generate low-salt soluble nucleosomes. Nearly quantitative recovery of chromatin is obtained with 600 mM NaCl; however, the remaining insoluble chromatin is enriched in actively transcribed regions. Salt-insoluble chromatin likely represents oligonucleosomes that are attached to large protein complexes. Both low-salt extracted and insoluble chromatin are rich in sequences that correspond to epigenetic regulatory elements genome-wide. The presence of active chromatin at both extremes of salt solubility suggests that these salt fractions capture bound and For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: tiling array analysis. BIOLOGICAL SOURCE: Cell Line: Kc167; Tissue: embryo-derived cell-line; Developmental Stage: late embryonic stage; Genotype: se/e; Sex: Female; NUMBER OF REPLICATES: 2; EXPERIMENTAL FACTORS: Cell Line Kc167; biochemical fraction (extract) precipitate; sodium chloride concentration (Compound) 600 mM; extraction time (sampling_time_point) 1 to 2 hours
2010-11-18 | E-GEOD-25389 | biostudies-arrayexpress