Marcel Edixhoven
Erasmus University Rotterdam
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Marcel Edixhoven.
Journal of Biological Chemistry | 1995
Pim J. French; Jan Bijman; Marcel Edixhoven; Arie B. Vaandrager; Bob J. Scholte; Suzanne M. Lohmann; Angus C. Nairn; Hugo R. de Jonge
Type II cGMP-dependent protein kinase (cGKII) isolated from pig intestinal brush borders and type Iα cGK (cGKI) purified from bovine lung were compared for their ability to activate the cystic fibrosis transmembrane conductance regulator (CFTR)-Cl− channel in excised, inside-out membrane patches from NIH-3T3 fibroblasts and from a rat intestinal cell line (IEC-CF7) stably expressing recombinant CFTR. In both cell models, in the presence of cGMP and ATP, cGKII was found to mimic the effect of the catalytic subunit of cAMP-dependent protein kinase (cAK) on opening CFTR-Cl− channels, albeit with different kinetics (2-3-min lag time, reduced rate of activation). By contrast, cGKI or a monomeric cGKI catalytic fragment was incapable of opening CFTR-Cl− channels and also failed to potentiate cGKII activation of the channels. The cAK activation but not the cGKII activation was blocked by a cAK inhibitor peptide. The slow activation by cGKII could not be ascribed to counteracting protein phosphatases, since neither calyculin A, a potent inhibitor of phosphatase 1 and 2A, nor ATPγS (adenosine 5′-O-(thiotriphosphate)), producing stable thiophosphorylation, was able to enhance the activation kinetics. Channels preactivated by cGKII closed instantaneously upon removal of ATP and kinase but reopened in the presence of ATP alone. Paradoxically, immunoprecipitated CFTR or CF-2, a cloned R domain fragment of CFTR (amino acids 645-835) could be phosphorylated to a similar extent with only minor kinetic differences by both isotypes of cGK. Phosphopeptide maps of CF-2 and CFTR, however, revealed very subtle differences in site-specificity between the cGK isoforms. These results indicate that cGKII, in contrast to cGKIα, is a potential activator of chloride transport in CFTR-expressing cell types.
Journal of Biological Chemistry | 1997
Arie B. Vaandrager; Ben C. Tilly; Albert Smolenski; Sonja Schneider-Rasp; Alice G. M. Bot; Marcel Edixhoven; Bob J. Scholte; Thomas Jarchau; Ulrich Walter; Suzanne M. Lohmann; Wolfgang Poller; Hugo R. de Jonge
In order to investigate the involvement of cGMP-dependent protein kinase (cGK) type II in cGMP-provoked intestinal Cl− secretion, cGMP-dependent activation and phosphorylation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channels was analyzed after expression of cGK II or cGK Iβ in intact cells. An intestinal cell line which stably expresses CFTR (IEC-CF7) but contains no detectable endogenous cGK II was infected with a recombinant adenoviral vector containing the cGK II coding region (Ad-cGK II) resulting in co-expression of active cGK II. In these cells, CFTR was activated by membrane-permeant analogs of cGMP or by the cGMP-elevating hormone atrial natriuretic peptide as measured by 125I− efflux assays and whole-cell patch clamp analysis. In contrast, infection with recombinant adenoviruses expressing cGK Iβ or luciferase did not convey cGMP sensitivity to CFTR in IEC-CF7 cells. Concordant with the activation of CFTR by only cGK II, infection with Ad-cGK II but not Ad-cGK Iβ enabled cGMP analogs to increase CFTR phosphorylation in intact cells. These and other data provide evidence that endogenous cGK II is a key mediator of cGMP-provoked activation of CFTR in cells where both proteins are co-localized, e.g. intestinal epithelial cells. Furthermore, they demonstrate that neither the soluble cGK Iβ nor cAMP-dependent protein kinase are able to substitute for cGK II in this cGMP-regulated function.
FEBS Letters | 1996
Ben C. Tilly; Matthias Gaestel; Katrin Engel; Marcel Edixhoven; Hugo R. de Jonge
Hypo‐osmotic swelling of human Intestine 407 cells leads to a significant increase of intracellular MAPKAP‐kinase 2 activity and Hsp27 phosphorylation. Pre‐treatment of the cells with the p38 MAP kinase inhibitor SB‐203580 blocks this activation, indicating that the hypotonicity‐induced activation of MAPKAP kinase 2 is, similarly to that described for hyper‐osmotic treatment, the result of an activated p38 MAP kinase cascade. The activation of MAPKAP kinase 2 proceeds with kinetics similar to that of one of the first physiological responses of hypo‐osmotic treatment, the opening of compensatory Cl− channels. However, inhibition of the p38 MAP kinase cascade does not block the osmo‐sensitive anion efflux and, vice versa, activation of p38 MAP kinase by cytokines and anisomycin does not increase the efflux. These results indicate that the p38 MAP kinase cascade is not directly involved in Cl− channel activation but instead may play a role in subsequent cellular repair processes.
Experimental Cell Research | 1991
André T. Hoogeveen; J. Keulemans; Rob Willemsen; Bob J. Scholte; Jan Bijman; Marcel Edixhoven; H. R. De Jonge; H. Galjaard
The recent identification of the cystic fibrosis (CF) gene and its putative protein product, the CF transmembrane conductance regulator (CFTR), enabled us to synthesize oligopeptides corresponding with a predicted extracellular domain (position 103-117; peptide A) and a cytoplasmic domain (position 501-515; peptide B) constituting the phenylalanine deletion (F 508) observed in the majority of CF mutations. Immunobiochemical studies with antibodies directed against these peptides revealed the presence of two CFTR candidate proteins (155 and 195 kDa) in various types of epithelial cells. Immunolocalization studies performed on slices of human duodenum showed the strongest expression in the endoplasmic reticulum (RER) of the mucus-producing Goblet cells. Labeling is also demonstrated in the RER and apical membranes of villus and crypt cells, however, to a weaker extent.
Clinica Chimica Acta | 1979
Wim Ruitenbeek; Marcel Edixhoven; H.R. Scholte
The stability of washed erythrocytes from patients with muscular dystrophy was determined in hypotonic phosphate buffered sodium chloride. Control cells were more stable than cells from Duchenne and myotonic patients. After pretreatment of the cells with phospholipase from pancreas, snake venom or bee venom in the presence of 14 mmol/l Ca2+, the order of osmotic stability in the 3 groups was not changed. In isotonic phosphate buffered NaCl, however, the erythrocytes of the myotonic patients were much more stable than the cells of the Duchenne and the control group. The lytic process was further studied in control cells with pancreatic phospholipase. 21 +/- 3 (S.E.M.) % of the cells were lysed. This process was (partly) prevented by omitting the phospholipase, by replacement of Na+ by K+ or Li+, by lowering the Ca2+ concentration, by omitting phosphate, by ouabain, by glucose, by ribose, by sucrose, by tetrodotoxin, a Na+-transport inhibitor. Blocking of the Ca2+ transport by La3+ or mersalyl, greatly stimulated the lytic process.
Journal of Biological Chemistry | 1993
Ben C. Tilly; N. Van Den Berghe; L. G. J. Tertoolen; Marcel Edixhoven; H. R. De Jonge
Molecular Biology of the Cell | 1996
Ben C. Tilly; Marcel Edixhoven; L. G. J. Tertoolen; N. Morii; Y. Saitoh; S. Narumiya; H. R. De Jonge
Proceedings of the National Academy of Sciences of the United States of America | 1998
Arie B. Vaandrager; Albert Smolenski; Ben C. Tilly; Adriaan B. Houtsmuller; Ehrich M. E. Ehlert; Alice G. M. Bot; Marcel Edixhoven; Wendy E. M. Boomaars; Suzanne M. Lohmann; Hugo R. de Jonge
Journal of Biological Chemistry | 1997
Arie B. Vaandrager; Marcel Edixhoven; Alice G. M. Bot; Marian A. Kroos; Thomas Jarchau; Suzanne M. Lohmann; Hans-Gottfried Genieser; Hugo R. de Jonge
American Journal of Physiology-cell Physiology | 1994
Ben C. Tilly; Marcel Edixhoven; N. Van Den Berghe; Alice G. M. Bot; H. R. De Jonge