PMID- 32045650
OWN - NLM
STAT- MEDLINE
DCOM- 20201214
LR  - 20201214
IS  - 1638-6183 (Electronic)
IS  - 0300-9084 (Linking)
VI  - 171-172
DP  - 2020 Apr-May
TI  - Hypoxia increases the rate of renal gluconeogenesis via hypoxia-inducible 
      factor-1-dependent activation of phosphoenolpyruvate carboxykinase expression.
PG  - 31-37
LID - S0300-9084(20)30020-1 [pii]
LID - 10.1016/j.biochi.2020.02.002 [doi]
AB  - Although up to 25% of glucose released into circulation in the postabsorptive 
      state comes from renal gluconeogenesis, the regulatory mechanisms of this process 
      are still poorly recognized, comparing to hepatic ones. The aim of the present 
      study was to examine if hypoxia-inducible factor-1 (HIF-1) might be involved in 
      the regulation of glucose de novo synthesis in kidneys. It was found that 
      HK-2 cells (immortalized human kidney proximal tubules, capable of 
      gluconeogenesis/glycogen synthesis) cultured with gluconeogenic substrates either 
      in hypoxia (1% O(2)) or in the presence of DMOG (an inhibitor of HIF-1alpha 
      degradation) exhibited increased glycogen content. This phenomenon was not 
      correlated with augmented glucose intake and the effects were reversed by 
      echinomycin (an inhibitor of HIF-1 binding to HRE sequence). As concluded from 
      the measurement of the intracellular content of gluconeogenic intermediates 
      followed by Western blot analysis, under conditions of hypoxia/increased HIF-1 
      level the activity of phosphoenolpyruvate carboxykinase (PEPCK) was elevated, as 
      a result of increased expression of the cytosolic isoform of PEPCK (PEPCK-C). 
      Chromatin immunoprecipitation (ChIP) analysis proved HIF-1 ability to bind to the 
      promoter region of PEPCK-C gene. The final conclusion that hypoxia/HIF-1 
      accelerates the rate of renal glucogenesis via the mechanism engaging activation 
      of PEPCK-C expression might be useful in terms of e.g. diabetes treatment, as it 
      is commonly accepted that under diabetic conditions kidneys and liver seem to be 
      equally important sources of glucose synthesized de novo.
CI  - Copyright (c) 2020 Elsevier B.V. and Societe Francaise de Biochimie et Biologie 
      Moleculaire (SFBBM). All rights reserved.
FAU - Owczarek, Aleksandra
AU  - Owczarek A
AD  - Department of Metabolic Regulation, Institute of Biochemistry, Faculty of 
      Biology, University of Warsaw, I. Miecznikowa 1, 02-096, Warsaw, Poland.
FAU - Gieczewska, Katarzyna
AU  - Gieczewska K
AD  - Department of Plant Anatomy and Cytology, Institute of Experimental Plant Biology 
      and Biotechnology, Faculty of Biology, University of Warsaw, I. Miecznikowa 1, 
      02-096, Warsaw, Poland.
FAU - Jarzyna, Robert
AU  - Jarzyna R
AD  - Department of Metabolic Regulation, Institute of Biochemistry, Faculty of 
      Biology, University of Warsaw, I. Miecznikowa 1, 02-096, Warsaw, Poland.
FAU - Jagielski, Adam K
AU  - Jagielski AK
AD  - Department of Metabolic Regulation, Institute of Biochemistry, Faculty of 
      Biology, University of Warsaw, I. Miecznikowa 1, 02-096, Warsaw, Poland.
FAU - Kiersztan, Anna
AU  - Kiersztan A
AD  - Department of Metabolic Regulation, Institute of Biochemistry, Faculty of 
      Biology, University of Warsaw, I. Miecznikowa 1, 02-096, Warsaw, Poland.
FAU - Gruza, Andrzej
AU  - Gruza A
AD  - Department of Metabolic Regulation, Institute of Biochemistry, Faculty of 
      Biology, University of Warsaw, I. Miecznikowa 1, 02-096, Warsaw, Poland.
FAU - Winiarska, Katarzyna
AU  - Winiarska K
AD  - Department of Metabolic Regulation, Institute of Biochemistry, Faculty of 
      Biology, University of Warsaw, I. Miecznikowa 1, 02-096, Warsaw, Poland. 
      Electronic address: k.winiarska@biol.uw.edu.pl.
LA  - eng
PT  - Journal Article
DEP - 20200208
PL  - France
TA  - Biochimie
JT  - Biochimie
JID - 1264604
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - EC 4.1.1.32 (PCK1 protein, human)
RN  - EC 4.1.1.32 (Phosphoenolpyruvate Carboxykinase (GTP))
RN  - EC 4.1.1.49 (PCK2 protein, human)
RN  - EC 4.1.1.49 (Phosphoenolpyruvate Carboxykinase (ATP))
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Cell Hypoxia
MH  - Cell Line
MH  - Gene Expression Regulation, Enzymologic
MH  - *Gluconeogenesis
MH  - Glucose/*metabolism
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*physiology
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Kidney/*metabolism
MH  - Phosphoenolpyruvate Carboxykinase (ATP)/*metabolism
MH  - Phosphoenolpyruvate Carboxykinase (GTP)/*metabolism
OTO - NOTNLM
OT  - Gluconeogenesis
OT  - Hypoxia
OT  - Hypoxia-inducible factor-1 (HIF-1)
OT  - Kidney
OT  - Phosphoenolpyruvate carboxykinase (PEPCK)
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/02/12 06:00
MHDA- 2020/12/15 06:00
CRDT- 2020/02/12 06:00
PHST- 2019/10/02 00:00 [received]
PHST- 2020/02/06 00:00 [accepted]
PHST- 2020/02/12 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/02/12 06:00 [entrez]
AID - S0300-9084(20)30020-1 [pii]
AID - 10.1016/j.biochi.2020.02.002 [doi]
PST - ppublish
SO  - Biochimie. 2020 Apr-May;171-172:31-37. doi: 10.1016/j.biochi.2020.02.002. Epub 
      2020 Feb 8.