scholarly journals Retraction Note to: Shear stress stimulates phosphorylation of protein kinase A substrate proteins including endothelial nitric oxide synthase in endothelial cells

2006 ◽  
Vol 38 (4) ◽  
pp. 453-453 ◽  
Author(s):  
Y C Boo
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Endothelial Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Substrate Proteins ◽  
Kinase A

LOW-INTENSITY ULTRASOUND INCREASES THE ENDOTHELIAL NITRIC OXIDE SYNTHASE (eNOS) EXPRESSION OF ENDOTHELIAL CELLS POSSIBLY VIA THE PHOSPHATIDYLINOSITOL 3-KINASE/AKT/PROTEIN KINASE A SIGNALING PATHWAY

2010 ◽  
Vol 22 (05) ◽  
pp. 367-376
Author(s):  
Shan-hui Hsu ◽  
Tsung-Bin Huang ◽  
Kuan-Pu Wang
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Ultrasound Exposure ◽  
Low Intensity ◽  
Low Intensity Ultrasound ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Kinase A

The stimulative effects and the associated mechanism of low-intensity ultrasound on endothelial cells were investigated in this study. Human umbilical cord endothelial cells (HUVECs) were exposed to 1 MHz pulsed ultrasound at 34 mW/cm2 for 10 min daily. The cell proliferation, nitric oxide release, intracellular calcium concentration, and endothelial nitric oxide synthase (eNOS) gene and protein expressions after ultrasound exposure were analyzed. It was found that ultrasound exposure did not change the cell proliferation, but it enhanced the release of nitric oxide and Ca2+ ions, and increased the eNOS activity. The induced phosphorylation of eNOS (Ser1177) by the ultrasound exposure was inhibited by the addition of N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline sulfonamide (H89, a protein kinase A inhibitor), but not 2-(4-morpholino)-8-phenyl-4H-1-benzopyran-4-one hydrochloride (LY294002, a phosphoatidylinositol 3-kinase inhibitor). The induced phosphorylation of Akt (protein kinase B, Ser473) by the ultrasound exposure was inhibited by the addition of LY294002, but not by the presence of H89. The results also applied to bovine carotid artery endothelial cells (BAECs) exposed to ultrasound at a larger intensity (68 mW/cm2). The above experiments suggested that low-intensity ultrasound may promote eNOS activity of endothelial cells via the phosphatidylinositol 3-kinase/Akt/protein kinase A signaling pathway. This may have implications on the therapeutic effect of ultrasound in tissue repair.

scholarly journals Endoplasmic Reticulum Ca2+ Release Modulates Endothelial Nitric-oxide Synthase via Extracellular Signal-regulated Kinase (ERK) 1/2-mediated Serine 635 Phosphorylation

2011 ◽  
Vol 286 (22) ◽  
pp. 20100-20108 ◽  
Author(s):  
Zhihong Xiao ◽  
Tingting Wang ◽  
Honghua Qin ◽  
Chao Huang ◽  
Youmei Feng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Nitric Oxide Synthase ◽  
Protein Phosphorylation ◽  
Endothelial Nitric Oxide Synthase ◽  
No Production ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Endothelial nitric-oxide synthase (eNOS) plays a central role in cardiovascular regulation. eNOS function is critically modulated by Ca2+ and protein phosphorylation, but the interrelationship between intracellular Ca2+ mobilization and eNOS phosphorylation is poorly understood. Here we show that endoplasmic reticulum (ER) Ca2+ release activates eNOS by selectively promoting its Ser-635/633 (bovine/human) phosphorylation. With bovine endothelial cells, thapsigargin-induced ER Ca2+ release caused a dose-dependent increase in eNOS Ser-635 phosphorylation, leading to elevated NO production. ER Ca2+ release also promoted eNOS Ser-633 phosphorylation in mouse vessels in vivo. This effect was independent of extracellular Ca2+ and selective to Ser-635 because the phosphorylation status of other eNOS sites, including Ser-1179 or Thr-497, was unaffected in thapsigargin-treated cells. Blocking ERK1/2 abolished ER Ca2+ release-induced eNOS Ser-635 phosphorylation, whereas inhibiting protein kinase A or Ca2+/calmodulin-dependent protein kinase II had no effect. Protein phosphorylation assay confirmed that ERK1/2 directly phosphorylated the eNOS Ser-635 residue in vitro. Further studies demonstrated that ER Ca2+ release-induced ERK1/2 activation mediated the enhancing action of purine or bradykinin receptor stimulation on eNOS Ser-635/633 phosphorylation in bovine/human endothelial cells. Mutating the Ser-635 to nonphosphorylatable alanine prevented ATP from activating eNOS in cells. Taken together, these studies reveal that ER Ca2+ release enhances eNOS Ser-635 phosphorylation and function via ERK1/2 activation. Because ER Ca2+ is commonly mobilized by agonists or physicochemical stimuli, the identified ER Ca2+-ERK1/2-eNOS Ser-635 phosphorylation pathway may have a broad role in the regulation of endothelial function.

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