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Identification of agents that reduce renal hypoxia-reoxygenation injury using cell-based screening: Purine nucleosides are alternative energy sources in LLC-PK1 cells during hypoxia.
MedLine Citation:
PMID:  22100704     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Acute tubular necrosis is a clinical problem that lacks specific therapy and is characterized by high mortality rate. The ischemic renal injury affects the proximal tubule cells causing dysfunction and cell death after severe hypoperfusion. We utilized a cell-based screening approach in a hypoxia-reoxygenation model of tubular injury to search for cytoprotective action using a library of pharmacologically active compounds. Oxygen-glucose deprivation (OGD) induced ATP depletion, suppressed aerobic and anaerobic metabolism, increased the permeability of the monolayer, caused poly(ADP-ribose) polymerase cleavage and caspase-dependent cell death. The only compound that proved cytoprotective either applied prior to the hypoxia induction or during the reoxygenation was adenosine. The protective effect of adenosine required the coordinated actions of adenosine deaminase and adenosine kinase, but did not requisite the purine receptors. Adenosine and inosine better preserved the cellular ATP content during ischemia than equimolar amount of glucose, and accelerated the restoration of the cellular ATP pool following the OGD. Our results suggest that radical changes occur in the cellular metabolism to respond to the energy demand during and following hypoxia, which include the use of nucleosides as an essential energy source. Thus purine nucleoside supplementation holds promise in the treatment of acute renal failure.
Authors:
Petra Szoleczky; Katalin Módis; Nóra Nagy; Zoltán Dóri Tóth; Douglas Dewitt; Csaba Szabó; Domokos Gerő
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-11
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  -     ISSN:  1096-0384     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Affiliation:
CellScreen Applied Research Center, Semmelweis University Medical School, Budapest, Hungary; Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX 77555-1102, USA.
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