PMID- 27252492
OWN - NLM
STAT- MEDLINE
DCOM- 20170724
LR  - 20220409
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 311
IP  - 4
DP  - 2016 Oct 1
TI  - Preconditioning mice with activators of AMPK ameliorates ischemic acute kidney 
      injury in vivo.
PG  - F731-F739
LID - 10.1152/ajprenal.00541.2015 [doi]
AB  - This study had two objectives: 1) to determine whether preconditioning cultured 
      proximal tubular cells (PTCs) with pharmacological activators of AMP-activated 
      protein kinase (AMPK) protects these cells from apoptosis induced by metabolic 
      stress in vitro and 2) to assess the effects of preconditioning mice with these 
      agents on the severity of ischemic acute renal kidney injury (AKI) in vivo. We 
      demonstrate that preconditioning PTCs with 
      5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) or A-769662 reduces 
      apoptosis of PTCs induced by subsequent stress. We also show that the reduction 
      in cell death during metabolic stress associated with pretreatment by AMPK 
      activators is associated with an increase in the cytosolic level of ATP, which is 
      mediated by an increase in the rate of glycolysis. In addition, we provide 
      evidence that the effect of AMPK activators on glycolysis is mediated, at least 
      in part, by an increased uptake of glucose, and by the induction of hexokinase II 
      (HK II) expression. Our data also show that the increased in HK II expression 
      associated with preconditioning with AMPK activators is mediated by the 
      activation (phosphorylation) of the cAMP-response element binding protein (CREB). 
      We also provide entirely novel evidence that that A-79662 is substantially more 
      effective than AICAR in mediating these alterations in PTCs in vitro. Finally, we 
      demonstrate that preconditioning mice with AICAR or A-769662 substantially 
      reduces the severity of renal dysfunction and tubular injury in a model of 
      ischemic AKI in vivo and that the efficacy of AICAR and A-768662 in ameliorating 
      ischemic AKI in vivo is comparable.
FAU - Lieberthal, Wilfred
AU  - Lieberthal W
AD  - Section of Nephrology, Department of Medicine, Stony Brook University Medical 
      Center, Stony Brook, New York; Section of Nephrology, Department of Medicine, 
      Northport Veterans Affairs Hospital, Northport, New York; 
      wilfred.lieberthal@stonybrookmedicine.edu.
FAU - Tang, Meiyi
AU  - Tang M
AD  - Section of Nephrology, Department of Medicine, Stony Brook University Medical 
      Center, Stony Brook, New York.
FAU - Lusco, Mark
AU  - Lusco M
AD  - Department of Pathology, Microbiology, and Immunology, Vanderbilt University 
      Medical Center, Nashville, Tennessee.
FAU - Abate, Mersema
AU  - Abate M
AD  - Section of Nephrology, Department of Medicine, Stony Brook University Medical 
      Center, Stony Brook, New York.
FAU - Levine, Jerrold S
AU  - Levine JS
AD  - Section of Nephrology, Department of Medicine, University of Illinois at Chicago, 
      Chicago, Illinois; Department of Microbiology and Immunology, University of 
      Illinois at Chicago, Chicago, Illinois; and Section of Nephrology, Department of 
      Medicine, Jesse Brown Veterans Affairs Hospital, Chicago, Illinois.
LA  - eng
PT  - Journal Article
DEP - 20160601
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Protective Agents)
RN  - 0 (Pyrones)
RN  - 0 (Ribonucleotides)
RN  - 0 (Thiophenes)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
RN  - P68477CD2C 
      (4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Acute Kidney Injury/drug therapy/metabolism/*prevention & control
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/pharmacology/therapeutic use
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Biphenyl Compounds
MH  - Ischemia/drug therapy/metabolism/*prevention & control
MH  - Ischemic Preconditioning/*methods
MH  - Kidney/*blood supply/drug effects/metabolism
MH  - Mice
MH  - Protective Agents/pharmacology/*therapeutic use
MH  - Pyrones/pharmacology/therapeutic use
MH  - Ribonucleotides/pharmacology/*therapeutic use
MH  - Thiophenes/pharmacology/therapeutic use
OTO - NOTNLM
OT  - AMP-activated protein kinase (AMPK)
OT  - apoptosis
OT  - glycolysis, hexokinases
OT  - ischemic AKI
EDAT- 2016/06/03 06:00
MHDA- 2017/07/25 06:00
CRDT- 2016/06/03 06:00
PHST- 2015/12/07 00:00 [received]
PHST- 2016/04/01 00:00 [accepted]
PHST- 2016/06/03 06:00 [pubmed]
PHST- 2017/07/25 06:00 [medline]
PHST- 2016/06/03 06:00 [entrez]
AID - ajprenal.00541.2015 [pii]
AID - 10.1152/ajprenal.00541.2015 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2016 Oct 1;311(4):F731-F739. doi: 
      10.1152/ajprenal.00541.2015. Epub 2016 Jun 1.