The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Protein kinase C beta II upregulates intercellular adhesion molecule-1 via mitochondrial activation in cultured endothelial cells

  • Joo, Hee Kyoung (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University) ;
  • Lee, Yu Ran (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University) ;
  • Choi, Sunga (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University) ;
  • Park, Myoung Soo (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University) ;
  • Kang, Gun (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University) ;
  • Kim, Cuk-Seong (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University) ;
  • Jeon, Byeong Hwa (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University)
  • Received : 2017.01.04
  • Accepted : 2017.05.03
  • Published : 2017.07.01
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Abstract

Activation of protein kinase C (PKC) is closely linked with endothelial dysfunction. However, the effect of $PKC{\beta}II$ on endothelial dysfunction has not been characterized in cultured endothelial cells. Here, using adenoviral $PKC{\beta}II$ gene transfer and pharmacological inhibitors, the role of $PKC{\beta}II$ on endothelial dysfucntion was investigated in cultured endothelial cells. Phorbol 12-myristate 13-acetate (PMA) increased reactive oxygen species (ROS), p66shc phosphorylation, intracellular adhesion molecule-1, and monocyte adhesion, which were inhibited by $PKC{\beta}i$ (10 nM), a selective inhibitor of $PKC{\beta}II$. PMA increased the phosphorylation of CREB and manganese superoxide dismutase (MnSOD), which were also inhibited by $PKC{\beta}i$. Gene silencing of CREB inhibited PMA-induced MnSOD expression, suggesting that CREB plays a key role in MnSOD expression. Gene silencing of $PKC{\beta}II$ inhibited PMA-induced mitochondrial ROS, MnSOD, and ICAM-1 expression. In contrast, overexpression of $PKC{\beta}II$ using adenoviral $PKC{\beta}II$ increased mitochondrial ROS, MnSOD, ICAM-1, and p66shc phosphorylation in cultured endothelial cells. Finally, $PKC{\beta}II$-induced ICAM-1 expression was inhibited by Mito-TEMPO, a mitochondrial ROS scavenger, suggesting the involvement of mitochondrial ROS in PKC-induced vascular inflammation. Taken together, the results suggest that $PKC{\beta}II$ plays an important role in PMA-induced endothelial dysfunction, and that the inhibition of $PKC{\beta}II$-dependent p66shc signaling acts as a therapeutic target for vascular inflammatory diseases.

Keywords

References

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