BIOMAT Database Logo BIOMAT Database Logo

Protein kinase Cdelta regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation. 2008

Neetu Sud, and Stephen Wedgwood, and Stephen M Black
Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd., CB-3210B, Augusta, GA 30912, USA.

In this study, we explore the roles of the delta isoform of PKC (PKCdelta) in the regulation of endothelial nitric oxide synthase (eNOS) activity in pulmonary arterial endothelial cells isolated from fetal lambs (FPAECs). Pharmacological inhibition of PKCdelta with either rottlerin or with the peptide, deltaV1-1, acutely attenuated NO production, and this was associated with a decrease in phosphorylation of eNOS at Ser1177 (S1177). The chronic effects of PKCdelta inhibition using either rottlerin or the overexpression of a dominant negative PKCdelta mutant included the downregulation of eNOS gene expression that was manifested by a decrease in both eNOS promoter activity and protein expression after 24 h of treatment. We also found that PKCdelta inhibition blunted Akt activation as observed by a reduction in phosphorylated Akt at position Ser473. Thus, we conclude that PKCdelta is actively involved in the activation of Akt. To determine the effect of Akt on eNOS signaling, we overexpressed a dominant negative mutant of Akt and determined its effect of NO generation, eNOS expression, and phosphorylation of eNOS at S1177. Our results demonstrated that Akt inhibition was associated with decreased NO production that correlated with reduced phosphorylation of eNOS at S1177, and decreased eNOS promoter activity. We next evaluated the effect of endogenously produced NO on eNOS expression by incubating FPAECs with the eNOS inhibitor 2-ethyl-2-thiopseudourea (ETU). ETU significantly inhibited NO production, eNOS promoter activity, and eNOS protein levels. Together, our data indicate involvement of PKCdelta-mediated Akt activation and NO generation in maintaining eNOS expression.

UI MeSH Term Description Entries
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D011651 Pulmonary Artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Arteries, Pulmonary,Artery, Pulmonary,Pulmonary Arteries
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005333 Fetus The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN. Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal
D000098 Acetophenones Derivatives of the simplest aromatic ketone acetophenone (of general formula C6H5C(O)CH3).
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001578 Benzopyrans Compounds with a core of fused benzo-pyran rings. Benzopyran,Chromene,Chromenes
D012756 Sheep Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS. Ovis,Sheep, Dall,Dall Sheep,Ovis dalli

Related Publications

Neetu Sud, and Stephen Wedgwood, and Stephen M Black
Retraction. Protein kinase Cδ regulates endothelial nitric oxide synthase expression via Akt activation and nitric oxide generation.
December 2011, American journal of physiology. Lung cellular and molecular physiology,
Neetu Sud, and Stephen Wedgwood, and Stephen M Black
Endothelin-1 impairs nitric oxide signaling in endothelial cells through a protein kinase Cdelta-dependent activation of STAT3 and decreased endothelial nitric oxide synthase expression.
November 2009, DNA and cell biology,
Neetu Sud, and Stephen Wedgwood, and Stephen M Black
Activation of endothelial nitric oxide synthase by cilostazol via a cAMP/protein kinase A- and phosphatidylinositol 3-kinase/Akt-dependent mechanism.
December 2006, Atherosclerosis,
Neetu Sud, and Stephen Wedgwood, and Stephen M Black
Protein kinase Cdelta regulates apoptosis via activation of STAT1.
October 2004, The Journal of biological chemistry,
Neetu Sud, and Stephen Wedgwood, and Stephen M Black
Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway.
January 2012, Free radical biology & medicine,
Neetu Sud, and Stephen Wedgwood, and Stephen M Black
Tetrahydrobiopterin regulates superoxide and nitric oxide generation by recombinant endothelial nitric oxide synthase.
August 1997, Biochemical and biophysical research communications,
Neetu Sud, and Stephen Wedgwood, and Stephen M Black
Activation of protein kinase B/Akt and endothelial nitric oxide synthase mediates agmatine-induced endothelium-dependent relaxation.
October 2007, European journal of pharmacology,
Neetu Sud, and Stephen Wedgwood, and Stephen M Black
Fas signaling induces Akt activation and upregulation of endothelial nitric oxide synthase expression.
April 2004, Hypertension (Dallas, Tex. : 1979),
Neetu Sud, and Stephen Wedgwood, and Stephen M Black
Relaxin up-regulates inducible nitric oxide synthase expression and nitric oxide generation in rat coronary endothelial cells.
February 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology,
Neetu Sud, and Stephen Wedgwood, and Stephen M Black
The Akt kinase signals directly to endothelial nitric oxide synthase.
January 1999, Current biology : CB,
Copied contents to your clipboard!