A5049172463- Autophagy in Disease and Therapy
- Cholesterol and Lipid Metabolism
- Atherosclerosis and Cardiovascular Diseases
- Diet and metabolism studies
- Metabolism and Genetic Disorders
- Metabolism, Diabetes, and Cancer
- Peroxisome Proliferator-Activated Receptors
- Endoplasmic Reticulum Stress and Disease
- Drug Transport and Resistance Mechanisms
- Glycogen Storage Diseases and Myoclonus
- Pancreatic function and diabetes
- Mitochondrial Function and Pathology
- Pharmacogenetics and Drug Metabolism
- CRISPR and Genetic Engineering
- PI3K/AKT/mTOR signaling in cancer
- Genomics, phytochemicals, and oxidative stress
- Cellular transport and secretion
- Inflammatory mediators and NSAID effects
- Advanced Proteomics Techniques and Applications
- Lipid metabolism and biosynthesis
- Adipokines, Inflammation, and Metabolic Diseases
- Barrier Structure and Function Studies
- Antioxidant Activity and Oxidative Stress
- Fungal and yeast genetics research
- Genetics, Aging, and Longevity in Model Organisms
University Medical Center Groningen
2016-2025
University of Groningen
2014-2025
Utrecht University
2006-2012
Abstract Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently mTORC1, activate other kinases mTOR network. To delineate aa-stimulated network dynamics, we here combine computational–experimental approach text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK),...
Extracts of plant adaptogens such as Eleutherococcus senticosus (or Acanthopanax senticosus) and Rhodiola rosea can increase stress resistance in several model systems. We now show that both extracts also the mean lifespan nematode C. elegans a dose-dependent way. In at least four independent experiments, 250 microg/ml (SHE-3) 10-25 (SHR-5) significantly increased life span between 10 20% (P < 0.001), maximum with 2-3 days postponed moment when first individuals population die, suggesting...
Cellular senescence is associated with cellular dysfunction and has been shown to occur in vivo age-related cardiovascular diseases such as atherosclerosis. Atherogenesis accompanied by intimal accumulation of LDL increased extravasation monocytes towards accumulated oxidized LDL, suggesting an affected barrier function vascular endothelial cells. Our objective was study the effect on non-senescent cells.Human umbilical vein cells were cultured until senescence. Senescent compared...
Atherosclerosis is a chronic inflammatory disease driven by hypercholesterolemia. During aging, T cells accumulate cholesterol, potentially affecting inflammation. However, the effect of cholesterol efflux pathways mediated ATP-binding cassette A1 and G1 (ABCA1/ABCG1) on cell-dependent age-related inflammation atherosclerosis remains poorly understood. In this study, we generate mice with cell-specific Abca1/Abcg1-deficiency low-density-lipoprotein-receptor deficient (Ldlr-/-) background....
Mechanistic target of rapamycin complex 1 (MTORC1) and polo like kinase (PLK1) are major drivers cancer cell growth proliferation, inhibitors both protein kinases currently being investigated in clinical studies. To date, MTORC1's PLK1's functions mostly studied separately, reports on their mutual crosstalk scarce. Here, we identify PLK1 as a physical MTORC1 interactor human cells. inhibition enhances activity under nutrient sufficiency starved cells, directly phosphorylates the component...
All cells and organisms exhibit stress-coping mechanisms to ensure survival. Cytoplasmic protein-RNA assemblies termed stress granules are increasingly recognized promote cellular survival under stress. Thus, they might represent tumor vulnerabilities that currently poorly explored. The translation-inhibitory eIF2α kinases established as main drivers of granule assembly. Using a systems approach, we identify the translation enhancers PI3K MAPK/p38 pro-stress-granule-kinases. They act through...
The intestine of children with severe malnutrition (SM) shows structural and functional changes that are linked to increased infection mortality. SM dysregulates the tryptophan-kynurenine pathway, which may impact processes such as SIRT1- mTORC1-mediated autophagy mitochondrial homeostasis. Using a mouse organoid model SM, we studied repercussions these dysregulations on enteropathy protective capacity maintaining activity health.SM was induced through feeding male weanling C57BL/6 mice low...
BACKGROUND: Smooth muscle cells (SMCs) regulate blood flow distribution via vasoconstriction mediated by α-ARs (α-adrenergic receptors). Plasma membrane cholesterol accumulation affects α 1 -AR signaling and promotes loss of SMC contractile markers in vitro. ABCA1 ABCG1 (ATP-binding cassette transporter A1 G1) mediate efflux to HDL (high-density lipoprotein). ABCA1/ABCG1 show high expression medial low intimal SMCs atherosclerotic plaques. The role SMC-mediated atherogenesis remains poorly...
In endothelial cells specifically, cPLA2α translocates from the cytoplasm to Golgi complex in response cell confluence. Considering link between confluence and cell–cell junction formation, emerging role of intracellular trafficking, we tested whether Golgi-associated is involved trafficking proteins. Here, show that redistribution correlates with adherens maturation occurs before tight formation. Disruption junctions using a blocking anti-VE-cadherin antibody reverses association Golgi....
Skeletal muscle insulin resistance is a key pathophysiological process that precedes the development of type 2 diabetes. Whereas an overload long-chain fatty acids can induce resistance, butyrate, short-chain acid (SCFA) produced from dietary fibre fermentation, prevents it. This preventive role butyrate has been attributed to histone deacetylase (HDAC)-mediated transcription regulation and activation mitochondrial fatty-acid oxidation. Here we address interplay between palmitate investigate...
Hospitalized children with severe malnutrition face high mortality rates and often suffer from hepatic intestinal dysfunction, negative impacts on their survival. New treatments cannot be developed without understanding the underlying pathophysiology. We have established characterized translational organoid models of liver intestine. In these models, amino acid starvation recapitulates expected organ-specific functional changes (e.g., steatosis, barrier dysfunction) accompanied by reduced...
Abstract Formaldehyde fixation is widely used for long‐term maintenance of tissue. However, due to formaldehyde‐induced crosslinks, fixed tissue proteins are difficult extract, which hampers mass spectrometry (MS) proteomic analyses. Recent years have seen the use different combinations high temperature and solubilizing agents (usually derived from antigen retrieval techniques) unravel formaldehyde‐fixed paraffin‐embedded proteomes. achieve protein extraction yields similar those...
Fasting hypoglycemia is a severe and incompletely understood symptom of various inborn errors metabolism (IEM). Precision-cut liver slices (PCLS) represent promising model for studying glucose production ex vivo. This study quantified the net human murine PCLS in presence different gluconeogenic precursors. Dihydroxyacetone-supplemented from fed mice yielded highest rate, further stimulated by forskolin dibutyryl-cAMP. Moreover, using
Defects in mitochondrial fatty acid β-oxidation (FAO) impair metabolic flexibility, which is an essential process for energy homeostasis. Very-long-chain acyl-CoA dehydrogenase (VLCADD; OMIM 609575) deficiency the most common long-chain FAO disorder presenting with hypoglycemia as a clinical manifestation. To prevent hypoglycemia, triheptanoin-a triglyceride composed of three heptanoates (C7) esterified glycerol backbone-can be used dietary treatment, since it metabolized into precursors...
<title>Abstract</title> Fasting hypoglycemia is a severe and incompletely understood symptom of various inborn errors metabolism (IEM). Precision-cut liver slices (PCLS) represent promising model to study glucose production ex vivo. This aimed provide comprehensive characterization in human murine PCLS. We quantified net rate PCLS derived the presence commonly used gluconeogenic precursors from fed fasted mice. Dihydroxyacetone (DHA) yielded highest rate, which was further stimulated by...
ABSTRACT Atherosclerosis is a chronic inflammatory disease driven by hypercholesterolemia. During aging, T-cells accumulate cholesterol, which could lead to pro-inflammatory phenotype. However, the role of cholesterol efflux pathways mediated ATP-binding cassette A1 and G1 (ABCA1/ABCG1) in T-cell-dependent age-related inflammation atherosclerosis remains poorly understood. In this study, we generated mice with T-cell-specific Abca1/Abcg1 -deficiency on low-density-lipoprotein-receptor...