PMID- 10646513
OWN - NLM
STAT- MEDLINE
DCOM- 20000210
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 74
IP  - 2
DP  - 2000 Feb
TI  - Chronic hypoxia enhances adenosine release in rat PC12 cells by altering
      adenosine metabolism and membrane transport.
PG  - 621-32
AB  - Acute exposure to hypoxia causes a release of adenosine (ADO) that is inversely
      related to the O2 levels in oxygen-sensitive pheochromocytoma (PC12) cells. In
      the current study, chronic exposure (48 h) of PC12 cells to moderate hypoxia (5% 
      O2) significantly enhanced the release of ADO during severe, acute hypoxia (1%
      O2). Investigation into the intra- and extracellular mechanisms underpinning the 
      secretion of ADO in PC12 cells chronically exposed to hypoxia revealed changes in
      gene expression and activities of several key enzymes associated with ADO
      production and metabolism, as well as the down-regulation of a nucleoside
      transporter. Decreases in the enzymatic activities of ADO kinase and ADO
      deaminase accompanied by an increase in those of cytoplasmic and
      ecto-5'-nucleotidases bring about an increased capacity to produce intra- and
      extracellular ADO. This increased potential to generate ADO and decreased
      capacity to metabolize ADO indicate that PC12 cells shift toward an ADO producer 
      phenotype during hypoxia. The reduced function of the rat equilibrative
      nucleoside transporter rENT1 also plays a role in controlling extracellular ADO
      levels. The hypoxia-induced alterations in the ADO metabolic enzymes and the
      rENT1 transporter seem to increase the extracellular concentration of ADO. The
      biological significance of this regulation is unclear but is likely to be
      associated with modulating cellular activity during hypoxia.
FAU - Kobayashi, S
AU  - Kobayashi S
AD  - Department of Molecular and Cellular Physiology, University of Cincinnati, Ohio
      45267-0576, USA.
FAU - Zimmermann, H
AU  - Zimmermann H
FAU - Millhorn, D E
AU  - Millhorn DE
LA  - eng
GR  - HL 55945/HL/NHLBI NIH HHS/United States
GR  - HL07571/HL/NHLBI NIH HHS/United States
GR  - R37 HL 33831/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Carrier Proteins)
RN  - 0 (Equilibrative Nucleoside Transporter 1)
RN  - 0 (Equilibrative-Nucleoside Transporter 2)
RN  - 0 (Membrane Proteins)
RN  - 0 (Slc29a1 protein, rat)
RN  - 0 (Slc29a2 protein, rat)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.1.20 (Adenosine Kinase)
RN  - EC 3.- (Hydrolases)
RN  - EC 3.1.3.5 (5'-Nucleotidase)
RN  - EC 3.3.1.1 (Adenosylhomocysteinase)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - 5'-Nucleotidase/metabolism
MH  - Adenosine/*metabolism
MH  - Adenosine Kinase/metabolism
MH  - Adenosine Triphosphate/metabolism
MH  - Adenosylhomocysteinase
MH  - Animals
MH  - Biological Transport/physiology
MH  - Carrier Proteins/metabolism
MH  - Cell Hypoxia/*physiology
MH  - Cell Membrane/metabolism
MH  - Cytoplasm/metabolism
MH  - Equilibrative Nucleoside Transporter 1
MH  - *Equilibrative-Nucleoside Transporter 2
MH  - Gene Expression/physiology
MH  - Hydrolases/genetics
MH  - Membrane Proteins/metabolism
MH  - PC12 Cells/*metabolism
MH  - Rats
MH  - Time Factors
MH  - Up-Regulation
EDAT- 2000/01/26 00:00
MHDA- 2000/01/26 00:01
CRDT- 2000/01/26 00:00
PHST- 2000/01/26 00:00 [pubmed]
PHST- 2000/01/26 00:01 [medline]
PHST- 2000/01/26 00:00 [entrez]
AID - 10.1046/j.1471-4159.2000.740621.x [doi]
PST - ppublish
SO  - J Neurochem. 2000 Feb;74(2):621-32. doi: 10.1046/j.1471-4159.2000.740621.x.