+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

B56α subunit of protein phosphatase 2A mediates retinoic acid-induced decreases in phosphorylation of endothelial nitric oxide synthase at serine 1179 and nitric oxide production in bovine aortic endothelial cells



B56α subunit of protein phosphatase 2A mediates retinoic acid-induced decreases in phosphorylation of endothelial nitric oxide synthase at serine 1179 and nitric oxide production in bovine aortic endothelial cells



Biochemical and Biophysical Research Communications 430(2): 476-481



We previously showed that all-trans retinoic acid (atRA) decreased nitric oxide (NO) production through Akt-mediated decreased phosphorylation of endothelial NO synthase at serine 1179 (eNOS-Ser(1179)) in bovine aortic endothelial cells (BAEC). Since protein phosphatase 2A (PP2A) was also reported to decrease eNOS-Ser(1179) phosphorylation, we investigated using BAEC whether PP2A mediates atRA-induced eNOS-Ser(1179) dephosphorylation and subsequent decreased NO production. Treatment with okadaic acid (5nM), a selective PP2A inhibitor, or ectopic expression of small interference RNA (siRNA) of PP2A catalytic subunit α (PP2A Cα) significantly increased eNOS-Ser(1179) phosphorylation and NO production. Each treatment also significantly reversed atRA-induced observed effects, suggesting a role for PP2A. We also found that atRA significantly increased cellular PP2A activity. However, Western blot analysis revealed that atRA did not increase the expression of PP2A Cα, although it significantly increased the level of B56α of PP2A regulatory B subunit (PP2A B56α), but not PP2A B55α and PP2A B56δ. Real-time PCR assay confirmed a significant increase in PP2A B56α mRNA expression in atRA-treated cells. Ectopic expression of siRNA of PP2A B56α significantly reversed atRA-induced inhibitory effects on eNOS-Ser(1179) phosphorylation and NO production, suggesting a role for PP2A B56α. Our study demonstrates for the first time that atRA decreases eNOS-Ser(1179) phosphorylation and NO release at least in part by increasing PP2A B56α-mediated PP2A activity in BAEC.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 036719271

Download citation: RISBibTeXText

PMID: 23237802

DOI: 10.1016/j.bbrc.2012.12.011


Related references

Retinoic acid decreases nitric oxide production in endothelial cells: a role of phosphorylation of endothelial nitric oxide synthase at Ser(1179). Biochemical and Biophysical Research Communications 326(4): 703-710, 2004

Endothelial cell superoxide anion radical generation is not dependent on endothelial nitric oxide synthase-serine 1179 phosphorylation and endothelial nitric oxide synthase dimer/monomer distribution. Free Radical Biology and Medicine 40(11): 2056-2068, 2006

Far-infrared radiation acutely increases nitric oxide production by increasing Ca(2+) mobilization and Ca(2+)/calmodulin-dependent protein kinase II-mediated phosphorylation of endothelial nitric oxide synthase at serine 1179. Biochemical and Biophysical Research Communications 436(4): 601-606, 2013

B56δ subunit of protein phosphatase 2A decreases phosphorylation of endothelial nitric oxide synthase at serine 116: Mechanism underlying aphidicolin-stimulated NO production. Nitric Oxide 50: 46-51, 2015

Serine 1179 phosphorylation of endothelial nitric oxide synthase caused by 2,4,6-trinitrotoluene through PI3K/Akt signaling in endothelial cells. Toxicology and Applied Pharmacology 214(1): 55-60, 2006

High glucose inhibits insulin-stimulated nitric oxide production without reducing endothelial nitric-oxide synthase Ser1177 phosphorylation in human aortic endothelial cells. Journal of Biological Chemistry 278(21): 18791-7, 2003

Arsenite Acutely Decreases Nitric Oxide Production via the ROS-Protein Phosphatase 1-Endothelial Nitric Oxide Synthase-Thr(497) Signaling Cascade. Biomolecules and Therapeutics 22(6): 510-518, 2014

Effect of tanshinone II A on angiotensin II induced nitric oxide production and endothelial nitric oxide synthase gene expression in cultured porcine aortic endothelial cells. Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi 27(7): 637-639, 2007

Inhibition of Endothelial Nitric Oxide Synthase Activity Through Phosphorylation by Protein Kinase C in Bovine Aortic Endothelial Cells. Circulation 90(4 Part 2): I628, 1994

Differential effects of heat shock protein 90 and serine 1179 phosphorylation on endothelial nitric oxide synthase activity and on its cofactors. Plos one 12(6): E0179978, 2017

Proinsulin C-peptide increases nitric oxide production by enhancing mitogen-activated protein-kinase-dependent transcription of endothelial nitric oxide synthase in aortic endothelial cells of Wistar rats. Diabetologia 46(12): 1698-1705, 2003

Phosphorylation of serine 1179 enhances superoxide generation from endothelial nitric oxide synthase. Circulation 108(17 Suppl.): IV-31, 2003

Localization of endothelial nitric-oxide synthase phosphorylated on serine 1179 and nitric oxide in Golgi and plasma membrane defines the existence of two pools of active enzyme. Journal of Biological Chemistry 277(6): 4277-4284, 2002

Chk1 and Hsp9 cooperatively regulate phosphorylation of endothelial nitric oxide synthase at serine 1179. 2011

Chk1 and Hsp90 cooperatively regulate phosphorylation of endothelial nitric oxide synthase at serine 1179. Free Radical Biology and Medicine 51(12): 2217-2226, 2011