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rdf:type |
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lifeskim:mentions |
umls-concept:C0006675,
umls-concept:C0006685,
umls-concept:C0030054,
umls-concept:C0205332,
umls-concept:C0242184,
umls-concept:C1150553,
umls-concept:C1325180,
umls-concept:C1325181,
umls-concept:C1418898,
umls-concept:C1444748,
umls-concept:C1879547
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pubmed:issue |
17
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pubmed:dateCreated |
2011-8-11
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pubmed:abstractText |
AMP-activated protein kinase (AMPK) is an energy sensor activated by increases in [AMP] or by oxidant stress (reactive oxygen species [ROS]). Hypoxia increases cellular ROS signaling, but the pathways underlying subsequent AMPK activation are not known. We tested the hypothesis that hypoxia activates AMPK by ROS-mediated opening of calcium release-activated calcium (CRAC) channels. Hypoxia (1.5% O(2)) augments cellular ROS as detected by the redox-sensitive green fluorescent protein (roGFP) but does not increase the [AMP]/[ATP] ratio. Increases in intracellular calcium during hypoxia were detected with Fura2 and the calcium-calmodulin fluorescence resonance energy transfer (FRET) sensor YC2.3. Antioxidant treatment or removal of extracellular calcium abrogates hypoxia-induced calcium signaling and subsequent AMPK phosphorylation during hypoxia. Oxidant stress triggers relocation of stromal interaction molecule 1 (STIM1), the endoplasmic reticulum (ER) Ca(2+) sensor, to the plasma membrane. Knockdown of STIM1 by short interfering RNA (siRNA) attenuates the calcium responses to hypoxia and subsequent AMPK phosphorylation, while inhibition of L-type calcium channels has no effect. Knockdown of the AMPK upstream kinase LKB1 by siRNA does not prevent AMPK activation during hypoxia, but knockdown of CaMKK? abolishes the AMPK response. These findings reveal that hypoxia can trigger AMPK activation in the apparent absence of increased [AMP] through ROS-dependent CRAC channel activation, leading to increases in cytosolic calcium that activate the AMPK upstream kinase CaMKK?.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AMP-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Monophosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ORAI1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/STIM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1098-5549
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3531-45
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pubmed:meshHeading |
pubmed-meshheading:21670147-AMP-Activated Protein Kinases,
pubmed-meshheading:21670147-Acetylcysteine,
pubmed-meshheading:21670147-Adenosine Monophosphate,
pubmed-meshheading:21670147-Animals,
pubmed-meshheading:21670147-Anoxia,
pubmed-meshheading:21670147-Blotting, Western,
pubmed-meshheading:21670147-Calcium,
pubmed-meshheading:21670147-Calcium Channels,
pubmed-meshheading:21670147-Calcium Signaling,
pubmed-meshheading:21670147-Calcium-Calmodulin-Dependent Protein Kinase Kinase,
pubmed-meshheading:21670147-Cell Hypoxia,
pubmed-meshheading:21670147-Cell Line, Tumor,
pubmed-meshheading:21670147-Cells, Cultured,
pubmed-meshheading:21670147-Endoplasmic Reticulum,
pubmed-meshheading:21670147-Enzyme Activation,
pubmed-meshheading:21670147-Fluorescence Resonance Energy Transfer,
pubmed-meshheading:21670147-Humans,
pubmed-meshheading:21670147-Lung,
pubmed-meshheading:21670147-Membrane Proteins,
pubmed-meshheading:21670147-Mice,
pubmed-meshheading:21670147-Mice, Knockout,
pubmed-meshheading:21670147-Neoplasm Proteins,
pubmed-meshheading:21670147-RNA Interference,
pubmed-meshheading:21670147-Rats,
pubmed-meshheading:21670147-Reactive Oxygen Species,
pubmed-meshheading:21670147-Thapsigargin
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pubmed:year |
2011
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pubmed:articleTitle |
Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels.
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pubmed:affiliation |
Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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