PMID- 14623077
OWN - NLM
STAT- MEDLINE
DCOM- 20031218
LR  - 20190621
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 554
IP  - 3
DP  - 2003 Nov 20
TI  - Hypoxic regulation of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 
      gene family (PFKFB-1-4) expression in vivo.
PG  - 264-70
AB  - When oxygen becomes limiting, cells shift primarily to a glycolytic mode for 
      generation of energy. A key regulator of glycolytic flux is 
      fructose-2,6-bisphosphate (F-2,6-BP), a potent allosteric regulator of 
      6-phosphofructo-1-kinase (PFK-1). The levels of F-2,6-BP are maintained by a 
      family of bifunctional enzymes, 
      6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB or PFK-2), which have 
      both kinase and phosphatase activities. Each member of the enzyme family is 
      characterized by their phosphatase:kinase activity ratio (K:B) and their 
      tissue-specific expression. Previous work demonstrated that one of the PFK-2 
      isozyme genes, PFKFB-3, was induced by hypoxia through the hypoxia-inducible 
      factor-1 (HIF-1) pathway. In this study we examined the basal and hypoxic 
      expression of three members of this family in different organs of mice. Our 
      findings indicate that all four isozymes (PFKFB-1-4) are responsive to hypoxia in 
      vivo. However, their basal level of expression and hypoxia responsiveness varies 
      in the different organs studied. Particularly, PFKFB-1 is highly expressed in 
      liver, heart and skeletal muscle, with the highest response to hypoxia found in 
      the testis. PFKFB-2 is mainly expressed in the lungs, brain and heart. However, 
      the highest hypoxia responses are found only in liver and testis. PFKFB-3 has a 
      variable low basal level of expression in all organs, except skeletal muscle, 
      where it is highly expressed. Most importantly, its hypoxia responsiveness is the 
      most ample of all three genes, being strongly induced in the lungs, liver, 
      kidney, brain, heart and testis. Further studies showed that PFKFB-1 and PFKFB-2 
      were highly responsive to hypoxia mimics such as transition metals, iron 
      chelators and inhibitors of HIF hydroxylases, suggesting that the hypoxia 
      responsiveness of these genes is also regulated by HIF proteins. In summary, our 
      data demonstrate that PFK-2 genes are responsive to hypoxia in vivo, indicating a 
      physiological role in the adaptation of the organism to environmental or 
      localized hypoxia/ischemia.
FAU - Minchenko, Oleksandr
AU  - Minchenko O
AD  - Department of Molecular Biology, Institute of Biochemistry, National Academy of 
      Science of Ukraine, Kiev 01601, Ukraine.
FAU - Opentanova, Iryna
AU  - Opentanova I
FAU - Caro, Jaime
AU  - Caro J
LA  - eng
GR  - R01 CA089212/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Isoenzymes)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 3G0H8C9362 (Cobalt)
RN  - EC 2.7.1.105 (PFKFB3 protein, human)
RN  - EC 2.7.1.105 (Phosphofructokinase-2)
RN  - J06Y7MXW4D (Deferoxamine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia/physiology
MH  - Cell Line, Tumor
MH  - Cobalt/pharmacology
MH  - DNA-Binding Proteins/metabolism
MH  - Deferoxamine/pharmacology
MH  - Enzyme Induction/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation, Enzymologic/drug effects/*physiology
MH  - Glycine/analogs & derivatives/pharmacology
MH  - HeLa Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Isoenzymes/biosynthesis/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nuclear Proteins/metabolism
MH  - Organ Specificity
MH  - Phosphofructokinase-2
MH  - *Protein Biosynthesis
MH  - Proteins/genetics
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - *Transcription Factors
EDAT- 2003/11/19 05:00
MHDA- 2003/12/19 05:00
CRDT- 2003/11/19 05:00
PHST- 2003/11/19 05:00 [pubmed]
PHST- 2003/12/19 05:00 [medline]
PHST- 2003/11/19 05:00 [entrez]
AID - S0014579303011797 [pii]
AID - 10.1016/s0014-5793(03)01179-7 [doi]
PST - ppublish
SO  - FEBS Lett. 2003 Nov 20;554(3):264-70. doi: 10.1016/s0014-5793(03)01179-7.