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Inhibition of mitochondrial respiration by nitric oxide rapidly stimulates cytoprotective GLUT3-mediated glucose uptake through 5′-AMP-activated protein kinase

Year: 2004
Type: article
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 Bolanos (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.
DOI: 10.1042/bj20040886
Language: English
Open Access status: bronze
OpenAlex ID: W1995061172
FWCI: 2.486
Cites: 45
Cited by: 82
Related to: 10