PMID- 22100704
OWN - NLM
STAT- MEDLINE
DCOM- 20120214
LR  - 20211021
IS  - 1096-0384 (Electronic)
IS  - 0003-9861 (Print)
IS  - 0003-9861 (Linking)
VI  - 517
IP  - 1
DP  - 2012 Jan 1
TI  - 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.
PG  - 53-70
LID - 10.1016/j.abb.2011.11.005 [doi]
AB  - 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.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Szoleczky, Petra
AU  - Szoleczky P
AD  - CellScreen Applied Research Center, Semmelweis University Medical School, 
      Budapest, Hungary; Department of Anesthesiology, The University of Texas Medical 
      Branch, Galveston, TX 77555-1102, USA.
FAU - Modis, Katalin
AU  - Modis K
FAU - Nagy, Nora
AU  - Nagy N
FAU - Dori Toth, Zoltan
AU  - Dori Toth Z
FAU - DeWitt, Douglas
AU  - DeWitt D
FAU - Szabo, Csaba
AU  - Szabo C
FAU - Gero, Domokos
AU  - Gero D
LA  - eng
GR  - R01 GM060915/GM/NIGMS NIH HHS/United States
GR  - R01GM060915/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111111
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Purine Nucleosides)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - IY9XDZ35W2 (Glucose)
RN  - K72T3FS567 (Adenosine)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adenosine/pharmacology
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Cell Hypoxia/drug effects
MH  - Cell Survival/drug effects
MH  - Cytoprotection/*drug effects
MH  - Glucose/metabolism
MH  - Hypoxia/*drug therapy/metabolism/pathology
MH  - Kidney/*cytology/*drug effects/metabolism/pathology
MH  - Kidney Tubular Necrosis, Acute/drug therapy/metabolism/pathology
MH  - LLC-PK1 Cells
MH  - Oxygen/metabolism
MH  - Purine Nucleosides/*pharmacology
MH  - Reperfusion Injury/*drug therapy/metabolism/pathology
MH  - Swine
PMC - PMC4676579
MID - NIHMS338295
EDAT- 2011/11/22 06:00
MHDA- 2012/02/15 06:00
PMCR- 2015/12/11
CRDT- 2011/11/22 06:00
PHST- 2011/08/10 00:00 [received]
PHST- 2011/11/01 00:00 [revised]
PHST- 2011/11/02 00:00 [accepted]
PHST- 2011/11/22 06:00 [entrez]
PHST- 2011/11/22 06:00 [pubmed]
PHST- 2012/02/15 06:00 [medline]
PHST- 2015/12/11 00:00 [pmc-release]
AID - S0003-9861(11)00363-8 [pii]
AID - 10.1016/j.abb.2011.11.005 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2012 Jan 1;517(1):53-70. doi: 10.1016/j.abb.2011.11.005. 
      Epub 2011 Nov 11.