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Polyethylene glycols interact with membrane glycerophospholipids: is this part of their mechanism for hypothermic graft protection?
Authors:Delphine Dutheil  Anja Underhaug Gjerde  Isabelle Petit-Paris  Gérard Mauco  Holm Holmsen
Affiliation:(1) Inserm U927, Poitiers, France;(2) Université de Poitiers, Faculté de Médecine et de Pharmacie, Poitiers, France;(3) CHU Poitiers, Laboratoire de Biochimie et Toxicologie, Poitiers, France;(4) Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway;(5) Present address: Hemarina SA, Morlaix, France
Abstract:Polyethylene glycol (PEG), a high-molecular-weight colloid present in new organ preservation solutions, protects against cold ischemia injuries leading to better graft function of transplanted organs. This protective effect cannot be totally explained by immuno-camouflaging property or signaling-pathway modifications. Therefore, we sought for an alternative mechanism dependent on membrane fluidity. Using the Langmuir–Pockles technique, we show here that PEGs interacted with lipid monolayers of defined composition or constituted by a renal cell lipid extract. High-molecular-weight PEGs stabilized the lipid monolayer at low surface pressure. Paradoxically, at high surface pressure, PEGs destabilized the monolayers. Hypothermia reduced the destabilization of saturated monolayer whereas unsaturated monolayer remained unaffected. Modification of ionic strength and pH induced a stronger stabilizing effect of PEG 35,000 Da which could explain its reported higher effectiveness on cold-induced injuries during organ transplantation. This study sheds a new light on PEG protective effects during organ preservation different from all classical hypotheses.
Keywords:Organ transplantation  Polyethylene Glycol  Hypothermia  Membrane Fluidity  Glycerophospholipid
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