Role of PKC-δ during Hypoxia in Heart-Derived H9c2 Cells

  • Kim Mi Jeong
    Department of Physiology, School of Medicine, Ajou University
  • Moon Chang-Hyun
    Department of Physiology, School of Medicine, Ajou University
  • Kim Mi-Young
    Department of Physiology, School of Medicine, Ajou University
  • Kim Min Hwa
    Department of Physiology, School of Medicine, Ajou University
  • Lee Soo Hwan
    Department of Physiology, School of Medicine, Ajou University
  • Baik Eun Joo
    Department of Physiology, School of Medicine, Ajou University
  • Jung Yi-Sook
    Department of Physiology, School of Medicine, Ajou University

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タイトル別名
  • Role of PKC-.DELTA. during Hypoxia in Heart-Derived H9c2 Cells
  • Role of PKC デルタ during Hypoxia in Heart Derived H9c2 Cells

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説明

In the present study, we investigated the role of protein kinase C (PKC) isoforms during hypoxia in heart-derived H9c2 cells. Hypoxia caused a rapid translocation of PKC-δ from soluble to particulate fraction and a downregulation of PKC-ε and PKC-ζ, whereas PKC-α and PKC-βI remained unaltered. When H9c2 cells were pretreated with PKC-δ inhibitor rottlerin (3 μM), hypoxia-induced apoptotic and necrotic cell death were significantly increased. Hypoxic insult also caused an activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK with no change in c-Jun NH2-terminal protein kinase (JNK) phosphorylation. Hypoxia-induced cell death was increased by treatment with ERK1/2 inhibitor U0126 (10 μM), but attenuated by p38 MAPK inhibitor SB202190 (10 μM). Treatment with rottlerin completely blocked the hypoxia-induced ERK phosphorylation, whereas it significantly increased p38 MAPK phosphorylation. The hypoxia-induced translocation of PKC-δ was not altered by U0126 and/or SB202190. From these results, it is suggested that hypoxia causes a rapid translocation of PKC-δ and subsequently ERK activation and p38 inactivation, rendering H9c2 cells resistant to hypoxia-induced cell death.<br>

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