PMID- 24990892
OWN - NLM
STAT- MEDLINE
DCOM- 20141021
LR  - 20211021
IS  - 1522-1466 (Electronic)
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 307
IP  - 4
DP  - 2014 Aug 15
TI  - Renal cortical hexokinase and pentose phosphate pathway activation through the 
      EGFR/Akt signaling pathway in endotoxin-induced acute kidney injury.
PG  - F435-44
LID - 10.1152/ajprenal.00271.2014 [doi]
AB  - While disruption of energy production is an important contributor to renal 
      injury, metabolic alterations in sepsis-induced AKI remain understudied. We 
      assessed changes in renal cortical glycolytic metabolism in a mouse model of 
      sepsis-induced AKI. A specific and rapid increase in hexokinase (HK) activity 
      ( approximately 2-fold) was observed 3 h after LPS exposure and maintained up to 18 h, in 
      association with a decline in renal function as measured by blood urea nitrogen 
      (BUN). LPS-induced HK activation occurred independently of HK isoform expression 
      or mitochondrial localization. No other changes in glycolytic enzymes were 
      observed. LPS-mediated HK activation was not sufficient to increase glycolytic 
      flux as indicated by reduced or unchanged pyruvate and lactate levels in the 
      renal cortex. LPS-induced HK activation was associated with increased 
      glucose-6-phosphate dehydrogenase activity but not glycogen production. 
      Mechanistically, LPS-induced HK activation was attenuated by pharmacological 
      inhibitors of the EGF receptor (EGFR) and Akt, indicating that 
      EGFR/phosphatidylinositol 3-kinase/Akt signaling is responsible. Our findings 
      reveal LPS rapidly increases renal cortical HK activity in an EGFR- and 
      Akt-dependent manner and that HK activation is linked to increased pentose 
      phosphate pathway activity.
CI  - Copyright (c) 2014 the American Physiological Society.
FAU - Smith, Joshua A
AU  - Smith JA
AD  - Department of Drug Discovery and Biomedical Sciences, Medical University of South 
      Carolina, Charleston, South Carolina; and.
FAU - Stallons, L Jay
AU  - Stallons LJ
AD  - Department of Drug Discovery and Biomedical Sciences, Medical University of South 
      Carolina, Charleston, South Carolina; and.
FAU - Schnellmann, Rick G
AU  - Schnellmann RG
AD  - Department of Drug Discovery and Biomedical Sciences, Medical University of South 
      Carolina, Charleston, South Carolina; and Ralph H. Johnson Veterans 
      Administration Medical Center, Charleston, South Carolina schnell@musc.edu.
LA  - eng
GR  - R01 GM084147/GM/NIGMS NIH HHS/United States
GR  - GM084147/GM/NIGMS NIH HHS/United States
GR  - UL1-RR029882/RR/NCRR NIH HHS/United States
GR  - C06-RR015455/RR/NCRR NIH HHS/United States
GR  - UL1 RR029882/RR/NCRR NIH HHS/United States
GR  - P20GM103542-02/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140702
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Heterocyclic Compounds, 3-Ring)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MK 2206)
RN  - 0 (Quinazolines)
RN  - EC 1.1.1.49 (Glucosephosphate Dehydrogenase)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.1 (HK1 protein, mouse)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Acute Kidney Injury/*physiopathology
MH  - Animals
MH  - Enzyme Activation/drug effects
MH  - ErbB Receptors/*physiology
MH  - Gefitinib
MH  - Glucosephosphate Dehydrogenase/metabolism
MH  - Glycolysis/drug effects
MH  - Heterocyclic Compounds, 3-Ring/pharmacology
MH  - Hexokinase/*metabolism
MH  - Kidney Cortex/drug effects/*physiology
MH  - Lipopolysaccharides
MH  - Male
MH  - Mice
MH  - Pentose Phosphate Pathway/*physiology
MH  - Phosphatidylinositol 3-Kinases
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Quinazolines/pharmacology
PMC - PMC4137133
OTO - NOTNLM
OT  - EGFR
OT  - acute kidney injury
OT  - hexokinase
OT  - lipopolysaccharide
OT  - pentose phosphate pathway
EDAT- 2014/07/06 06:00
MHDA- 2014/10/22 06:00
PMCR- 2015/08/15
CRDT- 2014/07/04 06:00
PHST- 2014/07/04 06:00 [entrez]
PHST- 2014/07/06 06:00 [pubmed]
PHST- 2014/10/22 06:00 [medline]
PHST- 2015/08/15 00:00 [pmc-release]
AID - ajprenal.00271.2014 [pii]
AID - F-00271-2014 [pii]
AID - 10.1152/ajprenal.00271.2014 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2014 Aug 15;307(4):F435-44. doi: 
      10.1152/ajprenal.00271.2014. Epub 2014 Jul 2.