Document Detail


Activation of AMP-activated protein kinase alpha1 alleviates endothelial cell apoptosis by increasing the expression of anti-apoptotic proteins Bcl-2 and survivin.
MedLine Citation:
PMID:  20233722     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Accumulating evidence suggests that AMP-activated protein kinase (AMPK) activation exerts anti-apoptotic effects in multiple types of cells. However, the underlying mechanisms remain poorly defined. The aim of the present study was to determine how AMPK suppresses apoptosis in endothelial cells exposed to hypoxia and glucose deprivation (OGD). AMPK activity, NF-kappaB activation, and endothelial cell apoptosis were assayed in cultured endothelial cells and mouse common carotid artery with or without OGD treatment. OGD markedly activated AMPK as early as 30 min, and AMPK activity reached maximal at 2 h of OGD. Endothelial apoptosis was not detected until 2 h of OGD but became markedly elevated at 6 h of OGD treatment. Furthermore, AMPK inhibition by Compound C or overexpression of dominant negative AMPK (AMPK-DN) exacerbated, whereas AMPK activation by pharmacologic (aminoimidazole carboxamide ribonucleotide (AICAR)) or genetic means (overexpression of constitutively active AMPK) suppressed endothelial cell apoptosis caused by OGD. Concomitantly, AMPK activation increased the expression of both Bcl-2 and Survivin, two potent anti-apoptotic proteins. Furthermore, AMPK activation significantly enhanced IkappaBalpha kinase activation, NF-kappaB nuclear translocation, and DNA binding activity of NF-kappaB. Consistently, selective inhibition of NF-kappaB, which abolished OGD-enhanced expression of Bcl-2 and Survivin, accentuated endothelial apoptosis caused by OGD. Finally, we found that genetic deletion of the AMPKalpha1, but not AMPKalpha2, suppressed OGD-enhanced NF-kappaB activation, the expression of Bcl-2 and Survivin, and endothelial apoptosis. Overall, our results suggest that AMPKalpha1, but not AMPKalpha2 activation, promotes cell survival by increasing NF-kappaB-mediated expression of anti-apoptotic proteins (Bcl-2 and Survivin) and intracellular ATP contents.
Authors:
Chao Liu; Bin Liang; Qilong Wang; Jiliang Wu; Ming-Hui Zou
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-03-16
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-10     Completed Date:  2010-06-14     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15346-55     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
AMP-Activated Protein Kinases / metabolism*
Animals
Blotting, Western
Cattle
Cells, Cultured
Electrophoretic Mobility Shift Assay
Endothelium, Vascular / cytology*,  enzymology,  metabolism
Enzyme Activation
Glucose / administration & dosage
In Situ Nick-End Labeling
Inhibitor of Apoptosis Proteins
Mice
Microtubule-Associated Proteins / metabolism*
NF-kappa B / metabolism
Oxygen / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism*
Repressor Proteins
Grant Support
ID/Acronym/Agency:
HL079584/HL/NHLBI NIH HHS; HL080499/HL/NHLBI NIH HHS; HL096032/HL/NHLBI NIH HHS; HL105157/HL/NHLBI NIH HHS; R01 HL105157/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Birc5 protein, mouse; 0/Inhibitor of Apoptosis Proteins; 0/Microtubule-Associated Proteins; 0/NF-kappa B; 0/Proto-Oncogene Proteins c-bcl-2; 0/Repressor Proteins; EC 2.7.11.1/AMP-Activated Protein Kinases; IY9XDZ35W2/Glucose; S88TT14065/Oxygen
Comments/Corrections

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