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Protein Kinase C (PKC) Delta Activator Attenuates NG-Nitro-L-Arginine-Methyl-Ester (L-NAME) Induced Leukocyte-Endothelial Interactions in Rat Mesenteric Post-Capillary Venules
Research Day
  • Hung Pham, Philadelphia College of Osteopathic Medicine
  • Amelie Bottex, Philadelphia College of Osteopathic Medicine
  • Amber Koon, Philadelphia College of Osteopathic Medicine
  • Jovan Adams, Philadelphia College of Osteopathic Medicine
  • Qian Chen, Philadelphia College of Osteopathic Medicine
  • Robert Barsotti, Philadelphia College of Osteopathic Medicine
  • Lindon Young, Philadelphia College of Osteopathic Medicine
Location
Philadelphia
Start Date
13-5-2015 1:00 PM
Description
Vascular endothelial dysfunction has been reported as the initial and critical step leading to inflammation-related diseases. It is characterized by reduced endothelial-derived nitric oxide (NO) and/or increased oxidative stress (i.e., superoxide (SO)), which leads to increased leukocyte-endothelial interactions. Endothelial dysfunction is attenuated by enhancing NO generation via endothelial NO synthase (eNOS) or by reducing SO release via inhibition of NADPH oxidase. PKC δ negatively regulates NADPH oxidase and reduces SO release, which will attenuate quenching of NO. The role of PKC δ on leukocyte endothelial interactions is unclear. This study examined these interactions, which are characterized by leukocyte rolling, adherence, and transmigration in rat mesenteric postcapillary venules via intravital microscopy. We found that superfusion of L-NAME (MW=270, 50μM, n=5) significantly augmented inflammation by inhibiting NO production via eNOS compared to Krebs’ buffer control (p<0.01, n=5). Conversely, PKC δ activator (Myr MRAAEDPM, MW=1130, 10 μM, n=4), a cell-permeable peptide, significantly attenuated L-NAME induced leukocyte-endothelial interactions (p<0.05). The preliminary data suggest that PKC δ activation may be an important mechanism in attenuating leukocyte-endothelial interactions induced by endothelial dysfunction. This study was supported by the Center for Chronic Disorders of Aging at PCOM.
Citation Information
Hung Pham, Amelie Bottex, Amber Koon, Jovan Adams, et al.. "Protein Kinase C (PKC) Delta Activator Attenuates NG-Nitro-L-Arginine-Methyl-Ester (L-NAME) Induced Leukocyte-Endothelial Interactions in Rat Mesenteric Post-Capillary Venules" (2015)
Available at: http://works.bepress.com/robert_barsotti/13/