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Inhibition of mitochondrial respiration by nitric oxide rapidly stimulates cytoprotective GLUT3-mediated glucose uptake through 5'-AMP-activated protein kinase
- Source :
- The Biochemical journal. 384(Pt 3)
- Publication Year :
- 2004
-
Abstract
- Recently, we have reported that the inhibition of mitochondrial respiration by nitric oxide (NO) leads to an up-regulation of glycolysis and affords cytoprotection against energy failure through the stimulation of AMPK (5′-AMP-activated protein kinase) [Almeida, Moncada and Bolaños (2004) Nat. Cell Biol. 6, 45–51]. To determine whether glucose transport contributes specifically to this effect, we have now investigated the possible role of NO in modulating glucose uptake through GLUT3, a facilitative high-affinity glucose carrier that has been suggested to afford cytoprotection against hypoglycaemic episodes. To do so, GLUT3-lacking HEK-293T cells (human embryonic kidney 293T cells) were transformed to express a plasmid construction encoding green fluorescent protein-tagged GLUT3 cDNA. This carrier was preferentially localized to the plasma membrane, was seen to be functionally active and afforded cytoprotection against low glucose-induced apoptotic death. Inhibition of mitochondrial respiration by NO triggered a rapid, cGMP-independent enhancement of GLUT3-mediated glucose uptake through a mechanism that did not involve transporter translocation. Furthermore, the functional disruption of AMPK by the RNA interference strategy rendered cells unable to respond to NO by activating GLUT3-mediated glucose uptake. These results suggest that the inhibition of mitochondrial respiration by NO activates AMPK to stimulate glucose uptake, thereby representing a novel survival pathway during pathophysiological conditions involving transient reductions in the supply of cellular glucose.
- Subjects :
- Snf3
Monosaccharide Transport Proteins
Glucose uptake
Cell Respiration
Apoptosis
Nerve Tissue Proteins
AMP-Activated Protein Kinases
Protein Serine-Threonine Kinases
Nitric Oxide
Biochemistry
5'-AMP-Activated Protein Kinase
Cell Line
Oxygen Consumption
AMP-activated protein kinase
Multienzyme Complexes
Animals
Humans
Molecular Biology
Cyclic GMP
biology
Glucose Transporter Type 3
Glucose transporter
AMPK
Cell Biology
Cytoprotection
Mitochondria
Rats
Protein Transport
Glucose
biology.protein
GLUT3
Research Article
Subjects
Details
- ISSN :
- 14708728
- Volume :
- 384
- Issue :
- Pt 3
- Database :
- OpenAIRE
- Journal :
- The Biochemical journal
- Accession number :
- edsair.doi.dedup.....d78f9e22c15dc48cd8e691cd13e46a85