Richard J Naftalin

Publications (124) View all

• Article: Aldosterone induces myofibroblast EGF secretion to regulate epithelial colonic permeability.

  Lluïsa Miró, Anna Pérez-Bosque, Mònica Maijó, Concepció Amat, Richard J Naftalin, Miquel Moretó
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  ABSTRACT: In vivo studies show that raised aldosterone (ALDO) during low-Na adaptation regulates the growth of pericryptal myofibroblasts and reduces the permeability of the colonic epithelium. The aim of this study was to reproduce in vitro the in vivo condition of increased ALDO using human CCD-18Co myofibroblasts and T84 colonic epithelial cells, in order to measure myofibroblast and epithelial proliferation and the expression of intercellular junction proteins. Proliferation was quantified by measuring 5-Bromo-2'-deoxyuridine incorporation. The myofibroblast expression of EGF, VEGFa and TGFβ1 was measured by real-time PCR and the expression of junctional complex proteins by Western blot. ALDO stimulated the proliferation of myofibroblasts by 70% (P<0.05) and increased EGF mRNA expression by 30% (P<0.05) without affecting VEGFa and TGFβ1. EGF concentration in the incubation medium increased by 30% (P<0.05) 24 hours after ALDO addition, and these effects were prevented by the addition of spironolactone. Myofibroblast proliferation in response to ALDO was mediated by EGFR and involved both MAPKK and PI3K pathways. Direct addition of ALDO to colonocytes did not affect the proliferation or expression of junctional complex proteins. However, exposing the T84 cells to an incubation medium of myofibroblasts with ALDO (conditioned medium) stimulated proliferation by 40% (P<0.05) and the expression of β-catenin and claudin IV by 30% (P<0.05). T84 proliferation decreased when α-EGF, or the EGFR antagonist AG1478, were present. These results support the view that changes in colonic permeability during low-Na adaptation are mediated by the EGF secreted by myofibroblasts in response to raised ALDO.
  AJP Cell Physiology 03/2013; · 3.54 Impact Factor
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  Available from: Richard J Naftalin

  Dataset: 272070a0

  B L Gupta, T A Hall, R J Naftalin
• Article: Water cotransport in pigmented epithelial cells.

  Richard Naftalin
  The Journal of Physiology 11/2010; 588(Pt 21):4063-4. · 4.72 Impact Factor
• Article: Quercetin-iron chelates are transported via glucose transporters.

  Evangelia Vlachodimitropoulou, Paul A Sharp, Richard J Naftalin
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  ABSTRACT: Flavonoids are well-known antioxidants and free radical scavengers. Their metal-binding activity suggests that they could be effective protective agents in pathological conditions caused by both extracellular and intracellular oxidative stress linked to metal overload. Quercetin is both a permeant ligand via glucose transport proteins (GLUTs) and a high-affinity inhibitor of GLUT-mediated glucose transport. Chelatable "free iron" at micromolar concentrations in body fluids is a catalyst of hydroxyl radical (OH(•)) production from hydrogen peroxide. A number of flavonoids, e.g., quercetin, luteolin, chrysin, and 3,6-dihydroxyflavone, have been demonstrated to chelate intracellular iron and suppress OH(•) radical production in Madin Darby canine kidney cells. The most effective chelation comes from the flavonone B ring catechol found in both quercetin and luteolin. We show here that quercetin concentrations of <1μM can facilitate chelatable iron shuttling via GLUT1 in either direction across the cell membrane. These siderophoric effects are inhibited by raised quercetin concentrations (>1μM) or GLUT inhibitors, e.g., phloretin or cytochalasin B, and iron efflux is enhanced by impermeant extracellular iron chelators, either desferrioxamine or rutin. This iron shuttling property of quercetin might be usefully harnessed in chelotherapy of iron-overload conditions.
  Free radical biology & medicine 01/2011; 50(8):934-44. · 5.42 Impact Factor
• Article: Reassessment of models of facilitated transport and cotransport.

  Richard J Naftalin
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  ABSTRACT: Most membrane transport models are determinate, requiring the transported ligand(s) to bind initially to a vacant site, which undergoes translation and releases ligand to the alternate side. The carrier reverts to its initial position to complete the net transport cycle. Ligand affinity may change during translation, but this must be compensated by an equivalent energy change(s) within the transport cycle. However, any asymmetric cyclic equilibrium deduced on this basis is thermodynamically fallacious. Determinate cotransport models imply lossless stoichiometric relationships between the complexed cotransported ligands. Independent ligand leakage apart from the mobile cotransport complex must occur outside the canonical cotransport pathway. In contrast, stochastic transport models assume independent ligand diffusion through a variably occluded channel(s) containing binding sites where ligands may undergo bimolecular exchanges. Energy dissipation is intrinsic to all stochastic transport models and occurs within the primary transport pathway. Frictional interactions within a shared path generate flow coupling between ligands. The primary driving forces causing transmembrane ligand flows are their electrochemical potential differences between the external solutions. Demonstrations that ligand exchanges in CLC and neurotransmitter transporters can be multimodal, encompassing both "channel"-like high and "transporter"-like lower conductance states and have independently regulated import and export exchange fluxes are major challenges to determinate models but are explicable by transient widening of a close-encounter region within the channel, leading to decreased coupling and enhanced efflux.
  Journal of Membrane Biology 03/2010; 234(2):75-112. · 1.81 Impact Factor