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TASK-1 Channel Promotes Hydrogen Peroxide Induced Apoptosis

Yun, Ji-Hyun    (Department of Physiology, College of Medicine, Chung-Ang University   ); Kim, Seung-Tae    (Department of Physiology, College of Medicine, Chung-Ang University   ); Bang, Hyo-Weon    (Department of Physiology, College of Medicine, Chung-Ang University  );
  • 초록

    Hydrogen peroxide ( $H_2O_2$ ) causes oxidative stress and is considered as an inducer of cell death in various tissues. Two-pore domain $K^+$ ( $K_{2p}$ ) channels may mediate $K^+$ efflux during apoptotic volume decreases (AVD) in zygotes and in mouse embryos. In the present study, we sought to elucidate linkage between $K_{2p}$ channels and cell death by $H_2O_2$ . Thus $K_{2p}$ channels (TASK-1, TASK-3, TREK-1, TREK-2) were stably transfected in HEK-293 cells, and cytotoxicity assay was preformed using cell counting kit-8 (CCK-8). Cell survival rates were calculated using the cytotoxicity assay data and dose-response curve was fitted to the $H_2O_2$ concentration. Ionic currents were recorded in cell-attached mode. The bath solution was the normal Ringer solution and the pipette solution was high $K^+$ solution. In HEK-293 cells expressing TREK-1, TREK-2, TASK-3, $H_2O_2$ induced cell death did not change in comparison to non-transfected HEK-293. In HEK-293 cells expressing TASK-1, however, dose-response curve was significantly shifted to the left. It means that $H_2O_2$ induced cell death was increased. In cell attached-mode recording, application of $H_2O_2$ (300μM) increased activity of all $K_{2p}$ channels. However, a low concentration of $H_2O_2$ ( $50{\mu}M$ ) increased only TASK-1 channel activity. These results indicate that TASK-1 might participate in $K^+$ efflux by $H_2O_2$ at low concentration, thereby inducing AVD.


  • 주제어

    Hydrogen peroxide .   Apoptosis .   $K_{2p}$ channels .   TASK-1 channel.  

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