The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Contradictory Effects of Superoxide and Hydrogen Peroxide on $K_{Ca}3.1$ in Human Endothelial Cells

  • Choi, Shinkyu (Department of Physiology and Medical Research Institute, School of Medicine, Ewha Womans University) ;
  • Na, Hye-Young (Department of Physiology and Medical Research Institute, School of Medicine, Ewha Womans University) ;
  • Kim, Ji Aee (Department of Physiology and Medical Research Institute, School of Medicine, Ewha Womans University) ;
  • Cho, Sung-Eun (Department of Physiology and Medical Research Institute, School of Medicine, Ewha Womans University) ;
  • Suh, Suk Hyo (Department of Physiology and Medical Research Institute, School of Medicine, Ewha Womans University)
  • Received : 2013.01.14
  • Accepted : 2013.05.20
  • Published : 2013.06.30
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Abstract

Reactive oxygen species (ROS) are generated in various cells, including vascular smooth muscle and endothelial cells, and regulate ion channel functions. $K_{Ca}3.1$ plays an important role in endothelial functions. However, the effects of superoxide and hydrogen peroxide radicals on the expression of this ion channel in the endothelium remain unclear. In this study, we examined the effects of ROS donors on $K_{Ca}3.1$ expression and the $K^+$ current in primary cultured human umbilical vein endothelial cells (HUVECs). The hydrogen peroxide donor, tert-butyl hydroperoxide (TBHP), upregulated $K_{Ca}3.1$ expression, while the superoxide donors, xanthine/xanthine oxidase mixture (X/XO) and lysophosphatidylcholine (LPC), downregulated its expression, in a concentration-dependent manner. These ROS donor effects were prevented by antioxidants or superoxide dismustase. Phosphorylated extracellular signal-regulated kinase (pERK) was upregulated by TBHP and downregulated by X/XO. In addition, repressor element-1-silencing transcription factor (REST) was downregulated by TBHP, and upregulated by X/XO. Furthermore, $K_{Ca}3.1$ current, which was activated by clamping cells with 1 ${\mu}M$ $Ca^{2+}$ and applying the $K_{Ca}3.1$ activator 1-ethyl-2-benzimidazolinone, was further augmented by TBHP, and inhibited by X/XO. These effects were prevented by antioxidants. The results suggest that hydrogen peroxide increases $K_{Ca}3.1$ expression by upregulating pERK and downregulating REST, and augments the $K^+$ current. On the other hand, superoxide reduces $K_{Ca}3.1$ expression by downregulating pERK and upregulating REST, and inhibits the $K^+$ current. ROS thereby play a key role in both physiological and pathological processes in endothelial cells by regulating $K_{Ca}3.1$ and endothelial function.

Keywords

References

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