By a News Reporter-Staff News Editor at Gene Therapy Weekly -- A new study on Small Interference RNAs (siRNAs) is now available. According to news reporting out of Madrid, Spain, by NewsRx editors, research stated, "ADP plays critical signaling roles in the vascular endothelium. ADP receptors are targeted by several cardiovascular drugs, yet the intracellular pathways modulated by ADP are incompletely understood."
Our news journalists obtained a quote from the research from Autonomous University, "These studies have identified important roles for the phosphatase PTEN in ADP-dependent modulation of the endothelial isoform of nitric oxide synthase (eNOS) as well as of lipid and protein kinase pathways in endothelial cells. We find that ADP-promoted eNOS activation as well as phosphorylation of p38 MAPK are enhanced by siRNA-mediated PTEN knockdown. However, the increase in ADP-dependent eNOS activation promoted by PIEN knockdown is abrogated by siRNA-mediated knockdown of p38 MAPK. These findings indicate that PTEN tonically suppresses both p38 phosphorylation as well as ADP-stimulated eNOS activity. A key enzymatic activity of PTEN is its role as a lipid phosphatase, catalyzing the dephosphorylation of phosphoinosito1-3,4,5-trisphosphate (PIP3) to phosphoinosito1-4,5-bisphosphate (PIP2). We performed biochemical analyses of cellular phospholipids in endothelial cells to show that siRNA-mediated PTEN knockdown leads to a marked increase in PIP3. Because these complex lipids activate the small GTPase Rac1, we explored the role of PTEN in ADP-modulated Racl activation. We used a FRET biosensor for Racl to show that ADP-dependent Racl activation is blocked by siRNA-mediated PTEN knockdown. We then exploited a FRET biosensor for PIP3 to show that the striking ADP-dependent increase in intracellular PIP3 is entirely blocked by PTEN knockdown."
According to the news editors, the research concluded: "These studies identify a key role for PTEN in the modulation of lipid mediators involved in ADP receptor-regulated endothelial signaling pathways involving eNOS activation in vascular endothelial cells."
For more information on this research see: Role of PTEN in modulation of ADP-dependent signaling pathways in vascular endothelial cells. Biochimica Et Biophysica Acta-Molecular Cell Research, 2013;1833(12):2586-2595. Biochimica Et Biophysica Acta-Molecular Cell Research can be contacted at: Elsevier Science Bv, PO Box 211, 1000 Ae Amsterdam, Netherlands (see also Small Interference RNAs (siRNAs)).
Our news journalists report that additional information may be obtained by contacting R. Breton-Romero, Autonomous University of Madrid, CSIC UAM, Center Biol Mol Severo Ochoa, E-28049 Madrid, Spain. Additional authors for this research include H. Kalwa, S. Lamas and T. Michel.
Keywords for this news article include: Spain, Madrid, Europe, Genetics, Biosensing, Bioengineering, Bionanotechnology, Endothelial Cells, Nanobiotechnology, Small Interference RNAs (siRNAs)
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