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B56 delta subunit of protein phosphatase 2A decreases phosphorylation of endothelial nitric oxide synthase at serine 116: Mechanism underlying aphidicolin-stimulated NO production

Title
B56 delta subunit of protein phosphatase 2A decreases phosphorylation of endothelial nitric oxide synthase at serine 116: Mechanism underlying aphidicolin-stimulated NO production
Authors
Park, Jung-HyunCho, Du-HyongLee, Jee YoungLee, Hyeon-JuHa, YenaAhn, Jung-HyuckJo, Inho
Ewha Authors
조인호안정혁이현주박정현
SCOPUS Author ID
조인호scopus; 안정혁scopus
Issue Date
2015
Journal Title
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
ISSN
1089-8603JCR Link1089-8611JCR Link
Citation
vol. 50, pp. 46 - 51
Keywords
Endothelial nitric oxide synthaseAphidicolinPhosphorylationProtein phosphatase 2APP2A B56 delta subunit
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
DNA damage is significant in endothelial cells (EC), particularly in anticancer chemotherapy. Here, we explored whether and how aphidicolin, a DNA-damaging chemical with a promising anticancer activity, alters NO production in bovine aortic endothelial cells (BAEC). In addition to increasing eNOS-Ser(1179) phosphorylation, aphidicolin decreased eNOS-Ser(116) phosphorylation with a concomitant increase in NO production in a time-dependent manner. The amino acid sequence around the eNOS-Ser116 residue was identified as the substrate site of the regulatory subunit B56 delta of protein phosphatase 2A (PP2A). As expected, okadaic acid, a specific PP2A inhibitor, reversed aphidicolin-induced eNOS-Ser(116) dephosphorylation in a dose-dependent manner. Aphidicolin also increased B56 delta-Ser(566) phosphorylation, although expression of neither the catalytic subunit C alpha (PP2A C alpha) nor B56 delta was altered. Ectopic expression of dominant negative (dn)-B56 delta reversed all of the observed effects of aphidicolin with respect to phosphorylation of eNOS-Ser(116) and B56 delta-Ser(566). Lastly, aphidicolin-stimulated NO production was also partially attenuated by ectopic expression of dn-B56 delta. Taken together, our results are the first to demonstrate that aphidicolin decreases phosphorylation of eNOS-Ser(116), at least in part by activating PP2A B56 delta, resulting in NO release in BAEC. (C) 2015 Elsevier Inc. All rights reserved.
DOI
10.1016/j.niox.2015.08.001
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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