cyclophilin b interacts with sodium-potassium atpase and is required for pump activity in proximal tubule cells of the kidney还有b与钠钾atp酶和泵需要交互活动在肾近端小管细胞.pdf

Cyclophilin B Interacts with Sodium-Potassium ATPase and Is Required for Pump Activity in Proximal Tubule Cells of the Kidney ˜ ´ 1 ´ 1 ´ 1 ´ ´ 1 3 Guillermo Sune , Eduard Sarro , Marta Puigmule , Joan Lopez-Hellın , Madeleine Zufferey , Thomas Pertel3, Jeremy Luban3, Anna Meseguer 1,2* ´ ´ 1 Fisiopatologıa Renal, Centre d’Investigacions en Bioquımica i Biologia Molecular (CIBBIM), Institut de Recerca Vall d’Hebron (VHIR), Hospital Universitari Vall d’Hebron, ´ Barcelona, Spain, 2 Departament de Bioquimica i Biologia Molecular, Facultat de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain, 3 Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland Abstract Cyclophilins (Cyps), the intracellular receptors for Cyclosporine A (CsA), are responsible for peptidyl-prolyl cis-trans isomerisation and for chaperoning several membrane proteins. Those functions are inhibited upon CsA binding. Albeit its great benefits as immunosuppressant, the use of CsA has been limited by undesirable nephrotoxic effects, including sodium retention, hypertension, hyperkalemia, interstial fibrosis and progressive renal failure in transplant recipients. In this report, we focused on the identification of novel CypB-interacting proteins to understand the role of CypB in kidney function and, in turn, to gain further insight into the molecular mechanisms of CsA-induced toxicity. By means of yeast two-hybrid screens with human kidney