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Träfflista för sökning "WFRF:(Andrén Per E.) ;pers:(Sandbaumhüter Friederike A)"

Sökning: WFRF:(Andrén Per E.) > Sandbaumhüter Friederike A

  • Resultat 1-6 av 6
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2.
  • Nezhyva, Mariya, et al. (författare)
  • POMC-specific Modulation of Metabolic and Immune Pathways via Melanocortin-3 Receptor Signaling
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • This proteomic study provides a nuanced understanding of the melanocortin-3 receptor (MC3R) and its ligand-specific effects on metabolic and immune pathways. Utilizing thermal proteome profiling with tandem mass spectrometry, we uncovered the distinct influences of adrenocorticotropic hormone (ACTH), α-melanocyte-stimulating hormone (α-MSH), and γ-melanocyte-stimulating hormone (γ-MSH) on protein thermal stability and pathway activation. ACTH uniquely affected NADPH-related metabolic proteins, α-MSH significantly modulated the IL-6 pathway via STAT3, and γ-MSH prominently activated interferon signaling. All ligands shared involvement in the cAMP-PKA-CREB and varied impacts on PI3K and ERK pathways, crucial for energy metabolism. Additionally, ligand-specific responses in mitochondrial protein stability suggest a role in cellular energy generation. 
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3.
  • Rofo, Fadi, et al. (författare)
  • Wide-Ranging Effects on the Brain Proteome in a Transgenic Mouse Model of Alzheimer's Disease Following Treatment with a Brain-Targeting Somatostatin Peptide
  • 2021
  • Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 12:13, s. 2529-2541
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer’s disease is the most common neurodegenerative disorder characterized by the pathological aggregation of amyloid-β (Aβ) peptide. A potential therapeutic intervention in Alzheimer’s disease is to enhance Aβ degradation by increasing the activity of Aβ-degrading enzymes, including neprilysin. The somatostatin (SST) peptide has been identified as an activator of neprilysin. Recently, we demonstrated the ability of a brain-penetrating SST peptide (SST-scFv8D3) to increase neprilysin activity and membrane-bound Aβ42 degradation in the hippocampus of mice overexpressing the Aβ-precursor protein with the Swedish mutation (APPswe). Using LC–MS, we further evaluated the anti-Alzheimer’s disease effects of SST-scFv8D3. Following a triple intravenous injection of SST-scFv8D3, the LC–MS analysis of the brain proteome revealed that the majority of downregulated proteins consisted of mitochondrial proteins regulating fatty acid oxidation, which are otherwise upregulated in APPswe mice compared to wild-type mice. Moreover, treatment with SST-scFv8D3 significantly increased hippocampal levels of synaptic proteins regulating cell membrane trafficking and neuronal development. Finally, hippocampal concentrations of growth-regulated α (KC/GRO) chemokine and degradation of neuropeptide-Y were elevated after SST-scFv8D3 treatment. In summary, our results demonstrate a multifaceted effect profile in regulating mitochondrial function and neurogenesis following treatment with SST-scFv8D3, further suggesting the development of Alzheimer’s disease therapies based on SST peptides.
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4.
  • Sandbaumhüter, Friederike A., et al. (författare)
  • Enantioselective CE–MS analysis of ketamine metabolites in urine
  • 2023
  • Ingår i: Electrophoresis. - : Wiley-VCH Verlagsgesellschaft. - 0173-0835 .- 1522-2683. ; 44:1-2, s. 125-134
  • Tidskriftsartikel (refereegranskat)abstract
    • The chiral drug ketamine has long-lasting antidepressant effects with a fast onset and is also suitable to treat patients with therapy-resistant depression. The metabolite hydroxynorketamine (HNK) plays an important role in the antidepressant mechanism of action. Hydroxylation at the cyclohexanone ring occurs at positions 4, 5, and 6 and produces a total of 12 stereoisomers. Among those, the four 6HNK stereoisomers have the strongest antidepressant effects. Capillary electrophoresis with highly sulfated γ-cyclodextrin (CD) as a chiral selector in combination with mass spectrometry (MS) was used to develop a method for the enantioselective analysis of HNK stereoisomers with a special focus on the 6HNK stereoisomers. The partial filling approach was applied in order to avoid contamination of the MS with the chiral selector. Concentration of the chiral selector and the length of the separation zone were optimized. With 5% highly sulfated γ-CD in 20 mM ammonium formate with 10% formic acid and a 75% filling the four 6HNK stereoisomers could be separated with a resolution between 0.79 and 3.17. The method was applied to analyze fractionated equine urine collected after a ketamine infusion and to screen the fractions as well as unfractionated urine for the parent drug ketamine and other metabolites, including norketamine and dehydronorketamine.
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5.
  • Sandbaumhuter, Friederike A., et al. (författare)
  • Label-Free Quantitative Thermal Proteome Profiling Reveals Target Transcription Factors with Activities Modulated by MC3R Signaling
  • 2023
  • Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 95:41, s. 15400-15408
  • Tidskriftsartikel (refereegranskat)abstract
    • Thermal proteome profiling with label-free quantitation using ion-mobility-enhanced LC-MS offers versatile data sets, providing information on protein differential expression, thermal stability, and the activities of transcription factors. We developed a multidimensional data analysis workflow for label-free quantitative thermal proteome profiling (TPP) experiments that incorporates the aspects of gene set enrichment analysis, differential protein expression analysis, and inference of transcription factor activities from LC-MS data. We applied it to study the signaling processes downstream of melanocortin 3 receptor (MC3R) activation by endogenous agonists derived from the proopiomelanocortin prohormone: ACTH, alpha-MSH, and gamma-MSH. The obtained information was used to map signaling pathways downstream of MC3R and to deduce transcription factors responsible for cellular response to ligand treatment. Using our workflow, we identified differentially expressed proteins and investigated their thermal stability. We found in total 298 proteins with altered thermal stability, resulting from MC3R activation. Out of these, several proteins were transcription factors, indicating them as being downstream target regulators that take part in the MC3R signaling cascade. We found transcription factors CCAR2, DDX21, HMGB2, SRSF7, and TET2 to have altered thermal stability. These apparent target transcription factors within the MC3R signaling cascade play important roles in immune responses. Additionally, we inferred the activities of the transcription factors identified in our data set. This was done with Bayesian statistics using the differential expression data we obtained with label-free quantitative LC-MS. The inferred transcription factor activities were validated in our bioinformatic pipeline by the phosphorylated peptide abundances that we observed, highlighting the importance of post-translational modifications in transcription factor regulation. Our multidimensional data analysis workflow allows for a comprehensive characterization of the signaling processes downstream of MC3R activation. It provides insights into protein differential expression, thermal stability, and activities of key transcription factors. All proteomic data generated in this study are publicly available at DOI: 10.6019/PXD039945.
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6.
  • Sandbaumhüter, Friederike A., et al. (författare)
  • Well-Plate muFASP for Proteomic Analysis of Single Pancreatic Islets
  • 2022
  • Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 21:4, s. 1167-1174
  • Tidskriftsartikel (refereegranskat)abstract
    • Filter-aided sample preparation (FASP) is widely used in bottom-upproteomics for tryptic digestion. However, the sample recovery yield of this methodis limited by the amount of the starting material. While similar to 100 ng of digested protein issufficient for thorough protein identification, proteomic information gets lost with aprotein content <10 mu g due to incomplete peptide recovery from thefilter. Wedeveloped and optimized aflexible well-plate mu FASP device and protocol that issuitable for an similar to 1 mu g protein sample. In 1 mu g of HeLa digest, we identified 1295 +/- 10proteins with mu FASP followed by analysis with liquid chromatography-massspectrometry. In contrast, only 524 +/- 5 proteins were identified with the standardFASP protocol, while 1395 +/- 4 proteins were identified in 20 mu g after standard FASPas a benchmark. Furthermore, we conducted a combined peptidomic and proteomicstudy of single pancreatic islets with well-plate mu FASP. Here, we separated neuropeptides and digested the remaining on-filterproteins for bottom-up proteomic analysis. Our results indicate inter-islet heterogeneity for the expression of proteins involved inglucose catabolism, pancreatic hormone processing, and secreted peptide hormones. We consider our method to provide a usefultool for proteomic characterization of samples where the biological material is scarce. All proteomic data are available under DOI:10.6019/PXD029039
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  • Resultat 1-6 av 6

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