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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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Endothelium specific matrilysin (MMP-7) expression in human cancers

Sier, C.F.M. (author), Hawinkels, L.J.A.C. (author), Zijlmans, H.J.M.A.A. (author), Zuidwijk, K. (author), Muller, E.S.M. (author), Ferreira, V. (author), Hanemaaijer, R. (author), Mulder-Stapel, A.A. (author), Kenter, G.G. (author), Verspaget, H.W. (author), Gorter, A. (author), TNO Kwaliteit van Leven (author)

Over-expression of matrilysin (MMP-7) is predominantly associated with epithelial (pre)malignant cells. In the present study MMP-7 expression is also found in endothelial cells in various human cancer types. Endothelial MMP-7 was associated with CD34 and/or CD105 expression. These immunohistochemical data were confirmed by RT-PCR on VEGF...

article 2008

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Dynamics of insulin signalling in liver during hyperinsulinemic euglycaemic clamp conditions in vivo and the effects of high-fat feeding in male mice

Korsheninnikova, E. (author), Voshol, P.J. (author), Baan, B. (author), van der Zon, G.C.M. (author), Havekes, L.M. (author), Romijn, J.A. (author), Maassen, J.A. (author), Ouwens, D.M. (author), TNO Kwaliteit van Leven (author)

Insulin is an important regulator of hepatic carbohydrate, lipid, and protein metabolism, and the regulation of these processes by insulin is disturbed under conditions of insulin resistance and type 2 diabetes. Despite these alterations, the impact of insulin resistance on insulin signalling in the liver is not well defined. Variations in time...

article 2007

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Cholesterol 7α-hydroxylase deficiency in mice on an APOE*3-Leiden background increases hepatic ABCA1 mRNA expression and HDL-cholesterol

Post, S.M. (author), Groenendijk, M. (author), van der Hoogt, C.C. (author), Fievet, C. (author), Luc, G. (author), Hoekstra, M. (author), Princen, H.M.G. (author), Staels, B. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)

OBJECTIVE - High-density lipoprotein (HDL) plays a key role in protection against development of atherosclerosis by reducing inflammation, protecting against LDL oxidation, and promoting reverse cholesterol transport from peripheral tissues to the liver for secretion into bile. Cholesterol 7α-hydroxylase (Cyp7a1) catalyzes the rate-limiting step...

article 2006

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Minoxidil exerts different inhibitory effects on gene expression of lysyl hydroxylase 1, 2, and 3: Implications for collagen cross-linking and treatment of fibrosis

Zuurmond, A.M. (author), Slot van der-Verhoeven, A.J. (author), van Dura, E.A. (author), de Groot, J. (author), Bank, R.A. (author), TNO Kwaliteit van Leven (author)

Collagen deposits in fibrotic lesions often display elevated levels of hydroxyallysine (pyridinoline) cross-links. The relation between the occurrence of pyridinoline cross-links and the irreversibility of fibrosis suggests that these cross-links contribute to the aberrant accumulation of collagen. Based on its inhibitory effect on lysyl...

article 2005

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Elevated formation of pyridinoline cross-links by profibrotic cytokines is associated with enhanced lysyl hydroxylase 2b levels

van der Slot, A.J. (author), van Dura, E.A. (author), de Wit, E.C. (author), de Groot, J. (author), Huizinga, T.W.J. (author), Bank, R.A. (author), Zuurmond, A.M. (author), TNO Preventie en Gezondheid (author)

The hallmark of fibrosis is the excessive accumulation of collagen. The deposited collagen contains increased pyridinoline cross-link levels due to an overhydroxylation of lysine residues within the collagen telopeptides. Lysyl hydroxylase 2b (LH2b) is the only lysyl hydroxylase consistently up-regulated in several forms of fibrosis, suggesting...

article 2005

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The cell wall stress response in Aspergillus niger involves increased expression of the glutamine: Fructose-6-phosphate amidotransferase-encoding gene (gfaA) and increased deposition of chitin in the cell wall

Ram, A.F.J. (author), Arentshorst, M. (author), Damveld, R.A. (author), van Kuyk, P.A. (author), Klis, F.M. (author), van den Hondel, C.A.M.J.J. (author), TNO Voeding (author)

Perturbation of cell wall synthesis in Saccharomyces cerevisiae, either by mutations in cell wall synthesis-related genes or by adding compounds that interfere with normal cell wall assembly, triggers a compensatory response to ensure cell wall integrity. This response includes an increase in chitin levels in the cell wall. Here it is shown that...

article 2004

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Endoplasmic reticulum stress leads to the selective transcriptional downregulation of the glucoamylase gene in Aspergillus niger

Al-Sheikh, H. (author), Watson, A.J. (author), Lacey, G.A. (author), Punt, P.J. (author), MacKenzie, D.A. (author), Jeenes, D.J. (author), Pakula, T. (author), Penttilä, M. (author), Alcocer, M.J.C. (author), Archer, D.B. (author), TNO Voeding (author)

We describe a new endoplasmic reticulum (ER)-associated stress response in the filamentous fungus Aspergillus niger. The inhibition of protein folding within the ER leads to cellular responses known collectively as the unfolded protein response (UPR) and we show that the selective transcriptional downregulation of the gene encoding glucoamylase,...

article 2004

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The role of the Aspergillus niger furin-type protease gene in processing of fungal proproteins and fusion proteins: Evidence for alternative processing of recombinant (fusion-) proteins

Punt, P.J. (author), Drint-Kuijvenhoven, A. (author), Lokman, B.C. (author), Spencer, J.A. (author), Jeenes, D. (author), Archer, D.A. (author), van den Hondel, C.A.M.J.J. (author)

We have characterized growth and protein processing characteristics of Aspergillus niger strains carrying a disrupted allele of the previously cloned and characterized kexB gene [Appl. Environ. Microbiol. 66 (2000) 363] encoding a furin-type endoprotease. Deletion of the single-copy gene confirms it to be non-essential but disruptant strains...

article 2003

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Moderate cholecalciferol supplementation depresses intestinal calcium absorption in growing dogs

Tryfonidou, M.A. (author), Stevenhagen, J.J. (author), van den Bemd, G.J.C.M. (author), Oosterlaken-Dijksterhuis, M.A. (author), Deluca, H.F. (author), Mol, J.A. (author), van den Brom, W.E. (author), van Leeuwen, J.P.T.M. (author), Hazewinkel, H.A.W. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Hormonal regulation of calcium (Ca) absorption was investigated in a cholecalciferol (vitamin D3)supplemented group (hVitD) vs. a control group (cVitD) of growing Great Danes (100 vs. 12.5 μg vitamin D3/kg diet). Although Ca intakes did not differ, fractional Ca absorption was significantly lower in the hVitD group than in the cVitD group. There...

article 2002

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Regulation of expression of the Aspergillus niger benzoate para-hydroxylase cytochrome P450 system

van den Brink, J.M. (author), Punt, P.J. (author), van Gorcom, R.F.M. (author), van den Hondel, C.A.M.J.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Cytochrome P450 enzyme systems are found throughout nature and are involved in many different, often complex, bioconversions. In the endoplasmic reticulum of the filamentous fungus Aspergillus niger a cytochrome P450 enzyme system is present that is capable of the para-hydroxylation of benzoate. The expression of the two genes encoding the...

article 2000

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Expression of heterologous genes in Schizophyllum commune is often hampered by the formation of truncated transcripts

Schuren, F.H.J. (author), Wessels, J.G.H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

GPD regulatory sequences were used to express a phleomycin resistance gene (Sh ble) in Schizophyllum commune, resulting in high numbers of phleomycin-resistant transformants. Attempts to express heterologous genes coding for hygromycin B phosphotransferase (hph), aminoglycoside phosphotransferase (apt), β-glucuronidase (uidA) and β-galactosidase...

article 1998

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The untranslated leader sequence of the barley lipoxygenase 1 (Lox1) gene confers embryo-specific expression

Rouster, J. (author), van Mechelen, J. (author), Cameron-Mills, V. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

The barley lipoxygenase 1 (Lox1) gene encodes a protein expressed in embryos during grain development and germination and in leaves after methyl-jasmonate (MeJA) treatment. Transient gene expression assays in germinating barley embryos were used to identify cis-regulatory elements involved in the embryo-specific expression of the Lox1 gene....

article 1998

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Insulin suppresses bile acid synthesis in cultured rat hepatocytes by down-regulation of cholesterol 7α-hydroxylase and sterol 27-hydroxylase gene transcription

Twisk, J. (author), Hoekman, M.F.M. (author), Lehmann, E.M. (author), Meijer, P. (author), Mager, W.H. (author), Princen, H.M.G. (author), TNO Preventie en Gezondheid (author)

Evidence from in vivo studies indicates that the bile acid pool and bile acid excretion are increased in humans with diabetes mellitus and in experimental diabetic animals, and that both parameters return to normal levels after administration of insulin. To investigate the biochemical background of these changes, the effects of insulin on bile...

article 1995

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Suppression of sterol 27-hydroxylase mRNA and transcriptional activity by bile acids in cultured rat hepatocytes

Twisk, J. (author), de Wit, E.C.M. (author), Princen, H.M.G. (author), TNO Preventie en Gezondheid (author)

In previous work we have demonstrated suppression of cholesterol 7α-hydroxylase by bile acids at the level of mRNA and transcription, resulting in a similar decline in bile acid synthesis in cultured rat hepatocytes. In view of the substantial contribution of the 'alternative' or '27-hydroxylase' route to total bile acid synthesis, as...

article 1995

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Heterogeneous expression of cholesterol 7α-hydroxylase and sterol 27- hydroxylase genes in the rat liver lobulus

Twisk, J. (author), Hoekman, M.F.M. (author), Mager, W.H. (author), Moorman, A.F.M. (author), de Boer, P.A.J. (author), Scheja, L. (author), Princen, H.M.G. (author), Gebhardt, R. (author), Instituut voor Verouderings- en Vaatziekten Onderzoek TNO (author)

We investigated the lobular localization and molecular level of expression of cholesterol 7α-hydroxylase and sterol 27-hydroxylase, two key enzymes in bile acid synthesis, in isolated periportal and pericentral hepatocytes and by in situ hybridization of rat liver. Enzyme activity, mRNA, and gene transcription of cholesterol 7α-hydroxylase were...

article 1995

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The effect of multiple copies of the upstream region of the Aspergillus niger glucoamylase-encoding gene on expression

Verdoes, J.C. (author), Punt, P.J. (author), Stouthamer, A.H. (author), van den Hondel, C.A.M.J.J. (author), Medisch Biologisch Laboratorium TNO Centraal Instituut voor Voedingsonderzoek TNO (author)

The regulation of transcription of the glucoamylase-encoding gene (glaA) of Aspergillus niger was studied. To facilitate this study a reporter strain containing a fusion of the glaA promoter (P(glaA)) of A. niger to the β- glucuronidase-encoding gene (uidA) of Escherichia coli was constructed. To analyze whether regulatory proteins are involved...

article 1994

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Glucoamylase overexpression in Aspergillus niger: Molecular genetic analysis of strains containing multiple copies of the glaA gene

Medisch Biologisch Laboratorium TNO (author), Verdoes, J.C. (author), Punt, P.J. (author), Schrickx, J.M. (author), van Verseveld, H.W. (author), Stouthamer, A.H. (author), van den Hondel, C.A.M.J.J. (author)

A strategy, based on the usage of the amdS selection marker and a cosmid vector containing four copies of the glucoamylase gene (glaA), was developed to obtain glucoamylase (GLA)-overproducing A. niger strains. With this strategy, fungal strains carrying up to 200 copies of the glaA gene could be isolated at a relatively high frequency. In each...

article 1993

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Translation controls the expression level of a chimaeric reporter gene

Hensgens, L.A.M. (author), Fornerod, M.W.J. (author), Rueb, S. (author), Winkler, A.A. (author), van der Veen, S. (author), Schilperoort, R.A. (author), Centrum voor Plantenfysiologisch Onderzoek (author)

Transcriptional and translational fusions between the reading frame of the β-D-glucuronidase gene (gusA) and the 2′ as well as the 1′ promoter of mannopine synthase (mas), a TR locus of Agrobacterium tumefaciens, were made. The expression of these constructs was studied in the transgenic F1 offspring of independent tobacco transformants at the...

article 1992