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Sex differences in skeletal muscle-aging trajectory: same processes, but with a different ranking

de Jong, J.C.B.C. (author), Attema, B.J. (author), van der Hoek, M.D. (author), Verschuren, L. (author), Caspers, M.P.M. (author), Kleemann, R. (author), van der Leij, F.R. (author), van den Hoek, A.M. (author), Nieuwenhuizen, A.G. (author), Keijer, J. (author)

Sex differences in muscle aging are poorly understood, but could be crucial for the optimization of sarcopenia-related interventions. To gain insight into potential sex differences in muscle aging, we recruited young (23 ± 2 years, 13 males and 13 females) and old (80 ± 3.5 years, 28 males and 26 females) participants. Males and females in both...

article 2023

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NF-B-mediated metabolic remodelling in the inflamed heart in acute viral myocarditis

Remels, A.H.V. (author), Derks, W.J.A. (author), Cillero-Pastor, B. (author), Verhees, K.J.P. (author), Kelders, M.C. (author), Heggermont, W. (author), Carai, P. (author), Summer, G. (author), Ellis, S.R. (author), de Theije, C.C. (author), Heeren, R.M.A. (author), Heymans, S. (author), Papageorgiou, A.P. (author), van Bilsen, M. (author)

Acute viral myocarditis (VM), characterised by leukocyte infiltration and dysfunction of the heart, is an important cause of sudden cardiac death in young adults. Unfortunately, to date, the pathological mechanisms underlying cardiac failure in VM remain incompletely understood. In the current study, we investigated if acute VM leads to cardiac...

article 2018

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Comprehensive analysis of the intracellular metabolism of antiretroviral nucleosides and nucleotides using liquid chromatography-tandem mass spectrometry and method improvement by using ultra performance liquid chromatography

Coulier, L. (author), Gerritsen, H. (author), van Kampen, J.J.A. (author), Reedijk, M.L. (author), Luider, T.M. (author), Osterhaus, A.D.M.E. (author), Gruters, R.A. (author), Brüll, L. (author)

Nucleoside reverse transcriptase inhibitors (NRTIs) are a key class of drugs for the treatment of HIV infection. NRTIs are intracellularly phosphorylated to their active triphosphate metabolites and compete with endogenous deoxynucleotides (dNTP) for substrate binding. It is therefore important to analyze the intracellular concentrations of...

article 2011

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Bace1 activity in cerebrospinal fluid and its relation to markers of ad pathology

Mulder, S.D. (author), van der Flier, W.M. (author), Verheijen, J.H. (author), Mulder, C. (author), Scheltens, P. (author), Blankenstein, M.A. (author), Hack, C.E. (author), Veerhuis, R. (author), TNO Kwaliteit van Leven (author)

Several studies have shown that reduced amyloid-β 1-42 (Aβ {42}) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. β-site APP cleaving enzyme (BACE1) is thought to be the major β-secretase involved in Aβ production in the brain, and therefore we investigated the relation...

article 2010

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DMBT1 functions as pattern-recognition molecule for poly-sulfated and poly-phosphorylated ligands

End, C. (author), Bikker, F.J. (author), Renner, M. (author), Bergmann, G. (author), Lyer, S. (author), Blaich, S. (author), Hudler, M. (author), Helmke, B. (author), Gassler, N. (author), Autschbach, F. (author), Ligtenberg, A.J.M. (author), Benner, A. (author), Holmskov, U. (author), Schirmacher, P. (author), Nieuw Amerongen, A.V. (author), Rosenstiel, P. (author), Sina, C. (author), Franke, A. (author), Hafner, M. (author), Kioschis, P. (author), Schreiber, S. (author), Poustka, A. (author), Mollenhauer, J. (author)

Deleted in malignant brain tumors 1 (DMBT1) is a secreted glycoprotein displaying a broad bacterial-binding spectrum. Recent functional and genetic studies linked DMBT1 to the suppression of LPS-induced TLR4-mediated NF-kappaB activation and to the pathogenesis of Crohn's disease. Here, we aimed at unraveling the molecular basis of its function...

article 2009

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Structure-function relationship of the human antimicrobial peptide LL-37 and LL-37 fragments in the modulation of TLR responses

TNO Defensie en Veiligheid (author), Molhoek, E.M. (author), den Hertog, A.L. (author), de Vries, A.M.B.C. (author), Nazmi, K. (author), Veerman, E.C.I. (author), Hartgers, F.C. (author), Yazdanbakhsh, M. (author), Bikker, F.J. (author), van der Kleij, D. (author)

Cathelicidins are effector molecules of the innate host defense system that establish an antimicrobial barrier at epithelial interfaces. The human cathelicidin LL-37, in addition to its antimicrobial activity, also exhibits immunomodulatory effects, such as inhibition of pro-inflammatory responses to bacterial LPS in human monocytic cells. In...

article 2009

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Simultaneous determination of endogenous deoxynucleotides and phosphorylated nucleoside reverse transcriptase inhibitors in peripheral blood mononuclear cells using ion-pair liquid chromatography coupled to mass spectrometry

Coulier, L. (author), van Kampen, J.J.A. (author), de Groot, R. (author), Gerritsen, H.W. (author), Bas, R.C. (author), van Dongen, W.D. (author), Brüll, L.P. (author), Luider, T.M. (author), TNO Kwaliteit van Leven (author), KvL (author)

Nucleoside reverse transcriptase inhibitors (NRTIs) are activated intracellularly to their triphosphate (TP) form, which compete with endogenous deoxynucleotide-triphosphates (dNTP) as substrate for HIV reverse transcriptase. The activity of NRTIs is thus described by the NRTI-TP to-dNTP ratio in relevant cell types. Therefore, we developed an...

article 2008

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Stress proteins in CNS inflammation

van Noort, J.M. (author), TNO Kwaliteit van Leven (author)

Stress proteins or heat shock proteins (HSPs) are ubiquitous cellular components that have long been known to act as molecular chaperones. By assisting proper folding and transport of proteins, and by assisting in the degradation of aberrant proteins, they play key roles in cellular metabolism. The frequent accumulation of insoluble protein...

article 2008

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Identification of multiple post-translational modifications in the porcine brain specific p25alpha

TNO Kwaliteit van Leven (author), Kleinnijenhuis, A.J. (author), Hedegaard, C. (author), Lundvig, D. (author), Sundbye, S. (author), Issinger, O.G. (author), Jensen, O.N. (author), Jensen, P.H. (author)

P25alpha is a protein normally expressed in oligodendrocytes and subcellular relocalization of p25alpha occurs in multiple system atrophy, Parkinson's disease and Lewy body dementia along with ectopic expression in neurons. Moreover, it accumulates in Lewy body inclusions with aggregated alpha-synuclein and is a potent stimulator of alpha...

article 2008

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Sustained activation of the mammalian target of rapamycin nutrient sensing pathway is associated with hepatic insulin resistance, but not with steatosis, in mice

Korsheninnikova, E. (author), van der Zon, G.C.M. (author), Voshol, P.J. (author), Janssen, G.M. (author), Havekes, L.M. (author), Grefhorst, A. (author), Kuipers, F. (author), Reijngoud, D.-J. (author), Romijn, J.A. (author), Ouwens, D.M. (author), Maassen, J.A. (author), TNO Kwaliteit van Leven (author)

Aims/hypothesis: Activation of nutrient sensing through mammalian target of rapamycin (mTOR) has been linked to the pathogenesis of insulin resistance. We examined activation of mTOR-signalling in relation to insulin resistance and hepatic steatosis in mice. Materials and methods: Chronic hepatic steatosis and hepatic insulin resistance were...

article 2006

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Endogenous interleukin-10 protects against hepatic steatosis but does not improve insulin sensitivity during high-fat feeding in mice

den Boer, M.A.M. (author), Voshol, P.J. (author), Schröder-van Der Elst, J.P. (author), Korsheninnikova, E. (author), Ouwens, D.M. (author), Kuipers, F. (author), Havekes, L.M. (author), Romijn, J.A. (author), TNO Kwaliteit van Leven (author)

Several studies have demonstrated an association in humans between plasma levels or production capacity of the antiinflammatory cytokine IL-10 and insulin sensitivity. The aim of our study was to investigate the protective role of endogenous IL-10 availability in the development of diet-induced insulin resistance. We compared parameters of...

article 2006

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Acute hepatic steatosis in mice by blocking β-oxidation does not reduce insulin sensitivity of very-low-density lipoprotein production

TNO Kwaliteit van Leven (author), Grefhorst, A. (author), Hoekstra, J. (author), Derks, T.G.J. (author), Ouwens, D.M. (author), Baller, J.F.W. (author), Havinga, R. (author), Havekes, L.M. (author), Romijn, J.A. (author), Kuipers, F. (author)

Accumulation of triglycerides (TG) in the liver is generally associated with hepatic insulin resistance. We questioned whether acute hepatic steatosis induced by pharmacological blockade of β-oxidation affects hepatic insulin sensitivity, i.e., insulin-mediated suppression of VLDL production and insulin-induced activation of phosphatidylinositol...

article 2005

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Involvement of furin-like proprotein convertases in the arterial response to injury

TNO Kwaliteit van Leven (author), Sluijter, J.P.G. (author), Verloop, R.E. (author), Pulskens, W.P.C. (author), Velema, E. (author), Grimbergen, J.M. (author), Quax, P.H. (author), Goumans, M.J. (author), Pasterkamp, G. (author), Kleijn, D.P.V.de (author)

Background: Furin-like proprotein convertases (PCs) are proteolytic activators of proproteins, like membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor beta (TGF-beta), that are described in the arterial response to injury. However, the involvement of furin-like PCs in the arterial response to injury has not been...

article 2005

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GIT1 Mediates Thrombin Signaling in Endothelial Cells: Role in Turnover of RhoA-Type Focal Adhesions

van Nieuw Amerongen, G.P. (author), Natarajan, K. (author), Yin, G. (author), Hoefen, R.J. (author), Osawa, M. (author), Haendeler, J. (author), Ridley, A.J. (author), Fujiwara, K. (author), van Hinsbergh, V.W.M. (author), Berk, B.C. (author), Gaubius Instituut TNO (author)

Thrombin mediates changes in endothelial barrier function and increases endothelial permeability. A feature of thrombin-enhanced endothelial hyperpermeability is contraction of endothelial cells (ECs), accompanied by formation of focal adhesions (FAs). Recently, a G protein-coupled receptor kinase-interacting protein, GIT1, was shown to regulate...

article 2004

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Global Suppression of IL-6-induced Acute Phase Response Gene Expression after Chronic in Vivo Treatment with the Peroxisome Proliferator-activated Receptor-alpha Activator Fenofibrate

TNO Preventie en Gezondheid (author), Gervois, P. (author), Kleemann, R. (author), Pilon, A. (author), Percevault, F. (author), Koenig, W. (author), Staels, B. (author), Kooistra, T. (author)

The peroxisome proliferator-activated receptor alpha (PPARalpha), which is highly expressed in liver, plays key roles in lipid metabolism and inflammation. Interleukin-6 (IL-6) is the principal inducer of acute phase response (APR) gene expression. In the present study, we demonstrate that chronic treatment with the PPARalpha agonist fenofibrate...

article 2004

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Increased hepatic insulin sensitivity together with decreased hepatic triglyceride stores in hormone-sensitive lipase-deficient mice

Voshol, P.J. (author), Haemmerle, G. (author), Ouwens, D.M. (author), Zimmermann, R. (author), Zechner, R. (author), Teusink, B. (author), Maassen, J.A. (author), Havekes, L.M. (author), Romijn, J.A. (author)

Hormone-sensitive lipase (HSL) is a major enzyme for triglyceride (TG) lipolysis in adipose tissue. In HSL-knockout mice, plasma free fatty acid and TG levels are low, associated with low liver TG content. Because a decreased hepatic insulin sensitivity has been reported to be associated with high liver TG levels, our aim was to determine...

article 2003

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A 16-Residue Peptide Fragment of Macrophage Migration Inhibitory Factor, MIF-(50-65), Exhibits Redox Activity and Has MIF-like Biological Functions

Gaubius Instituut TNO (author), Nguyen, M.T. (author), Beck, J. (author), Lue, H. (author), Fünfzig, H. (author), Kleemann, R. (author), Koolwijk, P. (author), Kapurniotu, A. (author), Bernhagen, J. (author)

Macrophage migration inhibitory factor (MIF) is a cytokine that participates in the host inflammatory response. A Cys-Xaa-Xaa-Cys (CXXC)-based thiol-protein oxidoreductase activity of MIF is associated with certain biological functions. Peptides spanning the CXXC region of thiol-protein oxidoreductases retain some biochemical properties of the...

article 2003

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Retrospective detection of exposure to organophosphorus anti-cholinesterases: Mass spectrometric analysis of phosphylated human butyrylcholinesterase

Fidder, A. (author), Hulst, A.G. (author), Noort, D. (author), de Ruiter, R. (author), van der Schans, M.J. (author), Benschop, H.P. (author), Langenberg, J.P. (author), Prins Maurits Laboratorium TNO (author)

In this paper a novel and general procedure is presented for detection of organophosphate-inhibited human butyrylcholinesterase (HuBuChE), which is based on electrospray tandem mass spectrometric analysis of phosphylated nonapeptides obtained after pepsin digestion of the enzyme. The utility of this method is exemplified by the positive analysis...

article 2002

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14-3-3 Proteins and a 13-lipoxygenase form associations in a phosphorylation-dependent manner

Holtman, W.L. (author), Roberts, M.R. (author), Wang, M. (author)

Recently, we have demonstrated by two different methods that lipoxgenases (LOXs) and 14-3-3 proteins form interactions in barley embryos [Holtman, Roberts, Oppedijk, Testerink, van Zeijl and Wang (2000) FEBS Lett. 474, 48-52]. It was shown by both co-immunoprecipitations and surface-plasmon resonance experiments that 13-LOX, but not 9-LOX, forms...

article 2000

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Dephosphorylation-induced structural changes in β-casein and its amphiphilic fragment in relation to emulsion properties

Darewicz, M. (author), Dziuba, J. (author), Caessens, P.W.J.R. (author), Gruppen, H. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)

To promote the understanding of the relationship between emulsifying and molecular properties of proteins/peptides, intact β-casein (βCN) and its amphipathic fragment, i.e. βCN (1-105/107) were dephosphorylated. Dephosphorylation was found not to change significantly their emulsifying properties. Since it is known that the structure of proteins...

article 2000