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(Pro)Renin Receptor Antagonism Attenuates High-Fat-Diet–Induced Hepatic Steatosis

Gayban, A.J.B. (author), Souza, L.A.C. (author), Cooper, S.G. (author), Regalado, E. (author), Kleemann, R. (author), Earley, Y.F. (author)

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver damage directly related to diabetes, obesity, and metabolic syndrome. The (pro)renin receptor (PRR) has recently been demonstrated to play a role in glucose and lipid metabolism. Here, we test the hypothesis that the PRR regulates the development of diet-induced hepatic...

article 2023

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A fungal biofilm reactor based on metal structured packing improves the quality of a Gla::GFP fusion protein produced by Aspergillus oryzae

Zune, Q. (author), Delepierre, A. (author), Gofflot, S. (author), Bauwens, J. (author), Twizere, J.C. (author), Punt, P.J. (author), Francis, F. (author), Toye, D. (author), Bawin, T. (author), Delvigne, F. (author)

Fungal biofilm is known to promote the excretion of secondary metabolites in accordance with solid-staterelated physiological mechanisms. This work is based on the comparative analysis of classical submerged fermentation with a fungal biofilmreactor for the production of a Gla::green fluorescent protein (GFP) fusion protein by Aspergillus oryzae...

article 2015

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The microtubule regulator stathmin is an endogenous protein agonist for TLR3.

Bsibsi, M. (author), Bajramovic, J.J. (author), Vogt, M.H. (author), van Duijvenvoorden, E. (author), Baghat, A. (author), Persoon-Deen, C. (author), Tielen, F. (author), Verbeek, R. (author), Huitinga, I. (author), Ryffel, B. (author), Kros, A. (author), Gerritsen, W.H. (author), Amor, S. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven (author)

TLR3 recognizes dsRNAs and is considered of key importance to antiviral host-defense responses. TLR3 also triggers neuroprotective responses in astrocytes and controls the growth of axons and neuronal progenitor cells, suggesting additional roles for TLR3-mediated signaling in the CNS. This prompted us to search for alternative, CNS-borne...

article 2010

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The dopamine receptor D2 agonist bromocriptine inhibits glucose-stimulated insulin secretion by direct activation of the α2-adrenergic receptors in beta cells

de Leeuw van Weenen, J.E. (author), Parlevliet, E.T. (author), Maechler, P. (author), Havekes, L.M. (author), Romijn, J.A. (author), Ouwens, D.M. (author), Pijl, H. (author), Guigas, B. (author), TNO Kwaliteit van Leven (author)

Treatment with the dopamine receptor D2 (DRD2) agonist bromocriptine improves metabolic features in obese patients with type 2 diabetes by a still unknown mechanism. In the present study, we investigated the acute effect of bromocriptine and its underlying mechanism(s) on insulin secretion both in vivo and in vitro. For this purpose, C57Bl6/J...

article 2010

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Time-resolved and tissue-specific systems analysis of the pathogenesis of insulin resistance

TNO Kwaliteit van Leven (author), Kleemann, R. (author), van Erk, M. (author), Verschuren, L. (author), van den Hoek, A.M. (author), Koek, M. (author), Wielinga, P.Y. (author), Jie, A. (author), Pellis, L. (author), Bobeldijk-Pastorova, I. (author), Kelder, T. (author), Toet, K. (author), Wopereis, S. (author), Cnubben, N. (author), Evelo, C. (author), van Ommen, B. (author), Kooistra, T. (author)

BACKGROUND: The sequence of events leading to the development of insulin resistance (IR) as well as the underlying pathophysiological mechanisms are incompletely understood. As reductionist approaches have been largely unsuccessful in providing an understanding of the pathogenesis of IR, there is a need for an integrative, time-resolved approach...

article 2010

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Doxycycline therapy for abdominal aneurysm: Improved proteolytic balance through reduced neutrophil content

Abdul-Hussien, H. (author), Hanemaaijer, R. (author), Verheijen, J.H. (author), van Bockel, J.H. (author), Geelkerken, R.H. (author), Lindeman, J.H.N. (author), TNO Kwaliteit van Leven (author)

Background: Matrix metalloproteinase-9 (MMP-9) is thought to play a central role in abdominal aortic aneurysm (AAA) initiation. Doxycycline, a tetracycline analogue, has direct MMP-9-inhibiting properties in vitro, and it effectively suppresses AAA development in rodents. Observed inhibition of AAA progression, and contradictory findings in...

article 2009

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Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm

Lindeman, J.H.N. (author), Abdul-Hussien, H. (author), Schaapherder, A.F.M. (author), van Bockel, J.H. (author), von der Thüsen, J.H. (author), Roelen, D.L. (author), Kleemann, R. (author)

Inflammation plays a key role in the pathogenesis of an AAA (abdominal aortic aneurysm); however, the nature of the inflammatory factors and cellular response(s) involved in AAA growth is controversial. In the present study, we set out to determine the aortic levels of inflammatory cytokines in relation to downstream inflammatory transcription...

article 2008

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Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: Implications for coeliac disease

Mitea, C. (author), Havenaar, R. (author), Wouter Drijfhout, J. (author), Edens, L. (author), Dekking, L. (author), Koning, F. (author), Dekking, E.H.A. (author), TNO Kwaliteit van Leven (author)

Background: Coeliac disease is caused by an immune response to gluten. As gluten proteins are proline rich they are resistant to enzymatic digestion in the gastrointestinal tract, a property that probably contributes to the immunogenic nature of gluten. Aims: This study determined the efficiency of gluten degradation by a post-proline cutting...

article 2008

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Transcriptome analysis provides new insights into liver changes induced in the rat upon dietary administration of the food additives butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole

Stierum, R. (author), Conesa, A. (author), Heijne, W. (author), Ommen, B.v. (author), Junker, K. (author), Scott, M.P. (author), Price, R.J. (author), Meredith, C. (author), Lake, B.G. (author), Groten, J. (author), TNO Kwaliteit van Leven (author), KvL (author)

Transcriptomics was performed to gain insight into mechanisms of food additives butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate (PG), and thiabendazole (TB), additives for which interactions in the liver can not be excluded. Additives were administered in diets for 28 days to Sprague-Dawley rats and cDNA microarray experiments were...

article 2008

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A guide to murine coagulation factor structure, function, assays, and genetic alterations

Emeis, J.J. (author), Jirouskova, M. (author), Muchitsch, E.-M. (author), Shet, A.S. (author), Smyth, S.S. (author), Johnson, G.J. (author), TNO Preventie en Gezondheid (author)

Murine blood coagulation factors and function are quite similar to those of humans. Because of this similarity and the adaptability of mice to genetic manipulation, murine coagulation factors and inhibitors have been extensively studied. These studies have provided significant insights into human hemostasis. They have also provided useful...

article 2007

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Expression of human α1-proteinase inhibitor in Aspergillus niger

Karnaukhova, E. (author), Ophir, Y. (author), Trinh, L. (author), Dalal, N. (author), Punt, P.J. (author), Golding, B. (author), Shiloach, J. (author), TNO Kwaliteit van Leven (author)

Background: Human α1-proteinase inhibitor (α1-PI), also known as antitrypsin, is the most abundant serine protease inhibitor (serpin) in plasma. Its deficiency is associated with development of progressive, ultimately fatal emphysema. Currently in the United States, α1-PI is available for replacement therapy as an FDA licensed plasma-derived (pd...

article 2007

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Xenobiotic metabolism in human skin and 3D human skin reconstructs: A review

Gibbs, S. (author), van de Sandt, J.J.M. (author), Merk, H.F. (author), Lockley, D.J. (author), Pendlington, R.U. (author), Pease, C.K. (author), TNO Kwaliteit van Leven (author)

In this review, we discuss and compare studies of xenobiotic metabolism in both human skin and 3D human skin reconstructs. In comparison to the liver, the skin is a less studied organ in terms of characterising metabolic capability. While the skin forms the major protective barrier to environmental chemical exposure, it is also a potential...

article 2007

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Determination of matrilysin activity in gastrointestinal neoplasia

Hawinkels, L.J.A.C. (author), Verspaget, H.W. (author), van den Berg, M. (author), Hanemaaijer, R. (author), Sier, C.F.M. (author), TNO Kwaliteit van Leven (author)

article 2007

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Identification of outer membrane proteins of Yersinia pestis through biotinylation

Smither, S.J. (author), Hill, J. (author), van Baar, B.L.M. (author), Hulst, A.G. (author), de Jong, A.L. (author), Titball, R.W. (author), TNO Defensie en Veiligheid (author)

The outer membrane of Gram-negative bacteria contains proteins that might be good targets for vaccines, antimicrobials or detection systems. The identification of surface located proteins using traditional methods is often difficult. Yersinia pestis, the causative agent of plague, was labelled with biotin. Tagged proteins were visualised through...

article 2007

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Human osteoblasts produce cathepsin K

Mandelin, J. (author), Hukkanen, M. (author), Li, T.F. (author), Korhonen, M. (author), Liljeström, M. (author), Sillat, T. (author), Hanemaaijer, R. (author), Salo, J. (author), Santavirta, S. (author), Konttinen, Y.T. (author), TNO Kwaliteit van Leven (author)

Healthy bone is a rigid yet living tissue that undergoes continuous remodeling. Osteoclasts resorb bone in the remodeling cycle. They secrete H+-ions and proteinases to dissolve bone mineral and degrade organic bone matrix, respectively. One of the main collagenolytic proteinase in osteoclasts is cathepsin K, a member of papain family cysteine...

article 2006

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Chemically modified tetracyclines stimulate matrix metalloproteinase-s production by periodontal ligament cells

Bildt, M.M. (author), Snoek-van Beurden, A.M.P. (author), de Groot, J. (author), van El, B. (author), Kuijpers-Jagtman, A.M. (author), van den Hoff, J.W. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Background and Objective: The purpose of this study was to investigate the effects of chemically modified tetracyclines (CMTs) on the production of gelatinases [matrix metalloproteinase (MMP)-2 and -9] by human periodontal ligament (PDL) cells, and on the activity of recombinant gelatinases. Material and Methods: Human PDL cells were cultured...

article 2006

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Detection of a soluble form of BACE-1 in human cerebrospinal fluid by a sensitive activity assay

TNO Kwaliteit van Leven (author), Verheijen, J.H. (author), Huisman, L.G.M. (author), van Lent, N. (author), Neumann, U. (author), Paganetti, P. (author), Erik Hack, C. (author), Bouwman, F. (author), Lindeman, J. (author), Bollen, E.L.E.M. (author), Hanemaaijer, R. (author)

Background: Formation of deposits of the insoluble amyloid β-peptide is believed to be causally related with neurodegeneration in Alzheimer disease (AD). The β-peptide originates from a larger amyloid precursor protein (APP) by the action of proteolytic enzymes. The first proteolytic event leading to amyloid formation is the cleavage of APP by...

article 2006

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Bile duct proliferation associated with bile salt-induced hypercholeresis in Mdr2 P-glycoprotein-deficient mice

Hulzebos, C.V. (author), Voshol, P.J. (author), Wolters, H. (author), Kruit, J.K. (author), Ottenhof, R. (author), Groen, A.K. (author), Stellaard, F. (author), Verkade, H.J. (author), Kuipers, F. (author), TNO Preventie en Gezondheid (author)

Background/Aims: Bile flow consists of bile salt-dependent bile flow (BSDF), generated by canalicular secretion of bile salts, and bile salt-independent flow (BSIF), probably of combined canalicular and ductular origin. Bile salt transport proteins have been identified in cholangiocytes, suggesting a role in control of BSDF and/or in control of...

article 2005

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Relevance of Ara h1, Ara h2 and Ara h3 in peanut-allergic patients, as determined by immunoglobulin E Western blotting, basophil-histamine release and intracutaneous testing: Ara h2 is the most important peanut allergen

Koppelman, S.J. (author), Wensing, M. (author), Ertmann, M. (author), Knulst, A.C. (author), Knol, E.F. (author), TNO Voeding (author)

Background: A number of allergenic proteins in peanut has been described and the relative importance of these allergens is yet to be determined. Objectives: We have investigated the relevance of previously identified peanut allergens in well-characterized peanut-allergic patients by in vitro, ex vivo and in vivo assays. Methods: Thirty-two adult...

article 2004

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Toll-Like Receptor 4 Is Involved in Outward Arterial Remodeling

Hollestelle, S.C.G. (author), de Vries, M.R. (author), van Keulen, J.K. (author), Schoneveld, A.H. (author), Vink, A. (author), Strijder, C.F. (author), van Middelaar, B.J. (author), Pasterkamp, G. (author), Q́uax, P.H.A. (author), de Kleijn, D.P.V. (author), TNO Preventie en Gezondheid (author)

Background-Toll-like receptor 4 (Tlr4) is the receptor for exogenous lipopolysaccharides (LPS). Expression of endogenous Tlr4 ligands, heat shock protein 60 (Hsp60) and extra domain A of fibronectin, has been observed in arthritic and oncological specimens in which matrix turnover is an important feature. In atherosclerosis, outward remodeling...

article 2004