Abstract |
Ability to adapt to conditions of limited nutrient supply requires a reorganization of the metabolic pathways to balance energy generation and production of biosynthetic intermediates. Several fast-growing cells overexpress the P2X7 receptor (P2X7R) for extracellular ATP. A feature of this receptor is to allow growth in the absence of serum. We show here that transfection of P2X7R allows proliferation of P2X7R-transfected HEK293 (HEK293-P2X7) cells not only in the absence of serum but also in low (4 mM) glucose, and increases lactate output compared with mock-transfected HEK293 (HEK293-mock) cells. In HEK293-P2X7, lactate output is further stimulated upon addition of exogenous ATP or the mitochondrial uncoupler carbonylcyanide p-trifluoromethoxyphenylhydrazone ( FCCP). In the human neuroblastoma cell line ACN, lactate output is also dependent on P2X7R function. P2X7R-expressing cells upregulate (a) the glucose transporter Glut1, (b) the glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase (G3PDH), (c) phosphofructokinase (PFK), (d) pyruvate kinase M2 (PKM2) and (e) pyruvate dehydrogenase kinase 1 (PDHK1); furthermore, P2X7R expression (a) inhibits pyruvate dehydrogenase (PDH) activity, (b) increases phosphorylated Akt/PKB and hypoxia-inducible factor 1α (HIF-1α) expression and (c) enhances intracellular glycogen stores. In HEK293-P2X7 cells, glucose deprivation increases lactate production, expression of glycolytic enzymes and ph-Akt/PKB level. These data show that the P2X7R has an intrinsic ability to reprogram cell metabolism to meet the needs imposed by adverse environmental conditions.
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Authors | F Amoroso, S Falzoni, E Adinolfi, D Ferrari, F Di Virgilio |
Journal | Cell death & disease
(Cell Death Dis)
Vol. 3
Pg. e370
(Aug 16 2012)
ISSN: 2041-4889 [Electronic] England |
PMID | 22898868
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Glucose Transporter Type 1
- Hypoxia-Inducible Factor 1, alpha Subunit
- Pyruvate Dehydrogenase Acetyl-Transferring Kinase
- Receptors, Purinergic P2X7
- Lactic Acid
- Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
- Adenosine Triphosphate
- Ketone Oxidoreductases
- Glyceraldehyde-3-Phosphate Dehydrogenases
- pyruvate dehydrogenase (NADP+)
- Phosphofructokinases
- Pyruvate Kinase
- 3-Phosphoinositide-Dependent Protein Kinases
- Protein Serine-Threonine Kinases
- Proto-Oncogene Proteins c-akt
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Topics |
- 3-Phosphoinositide-Dependent Protein Kinases
- Adenosine Triphosphate
(pharmacology)
- Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
(chemistry, pharmacology)
- Cell Line, Tumor
- Glucose Transporter Type 1
(genetics, metabolism)
- Glyceraldehyde-3-Phosphate Dehydrogenases
(genetics, metabolism)
- Glycolysis
(drug effects)
- HEK293 Cells
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit
(genetics, metabolism)
- Ketone Oxidoreductases
(genetics, metabolism)
- Lactic Acid
(metabolism)
- Phosphofructokinases
(genetics, metabolism)
- Protein Serine-Threonine Kinases
(genetics, metabolism)
- Proto-Oncogene Proteins c-akt
(genetics, metabolism)
- Pyruvate Dehydrogenase Acetyl-Transferring Kinase
- Pyruvate Kinase
(genetics, metabolism)
- Receptors, Purinergic P2X7
(metabolism)
- Transfection
- Up-Regulation
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