Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Phospholipase D Activity is Elevated in Hepatitis C Virus Core Protein-Transformed NIH 3T3 Mouse Fibroblast Cells

C형 간염바이러스의 core 단백질에 의해 암화된 쥐의 섬유아세포에서 phospholipase D 효소활성의 증가

  • Kim, Joonmo (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Jung, Eun-Young (Department of Microbiology, College of Natural Sciences, Pusan National University) ;
  • Jang, Kyung-Lib (Department of Microbiology, College of Natural Sciences, Pusan National University) ;
  • Min, Do-Sik (Department of Physiology, College of Medicine, The Catholic University of Korea)
  • Published : 2003.10.01
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Abstract

Hepatitis C Virus (HCV) is associated with a severe liver disease and increased frequency in the development of hepatocellular carcinoma. Overexpression of HCV core protein is known to transform fibroblast cells. Phospholipase D (PLD) activity is commonly elevated in response to mitogenic signals, and PLD has been also reported to be overexpressed and hyperactivated in some human cancer. The aim of this study was to understand how PLD can be regulated in HCV core protein-transformed NIH3T3 mouse fibroblast cells. We observed that in unstimulated state, basal PLD activity was higher in NIH3T3 cells overexpressing HCV core protein than in vector-transfected cells. Although expression of PLD and protein kinase C (PKC) in core protein-transformed cells was similar with that of control cells, phorbol 12-myristate 13-acetate (PMA), which is known to activate PKC, stimulated significantly PLD activity in core protein-transformed cells, compared with that of the control cells. PLD activity assay using PKC isozyme-specific inhibitor, and PKC translocation experiment showed that PKC-$\delta$ was mainly involved in the PMA-induced PLD activation in the core-transformed cells. Taken together, these results suggest that PLD might be implicated in core protein-induced transformation.

C형 간염바이러스는 간암을 야기하는 심각한 바이러스이다. C형 간염바이러스의 core 단백질의 과발현은 섬유아세포를 암화시키는 것으로 알려져 있다. Phospholipase D (PLD)의 효소활성이 세포증식 신호전달에 의해 활성화되어 있으며, 사람의 암조직에서 과발현 및 활성이 증가되어 있는 것으로 알려져 있다. 본 연구의 목적은, core 단백질에 의해 암화된 세포에서 PLD가 어떻게 조절되는지를 이해하고자 하는 것이다. 자극이 없는 상태에서뿐만 아니라 PMA에 의해 유도되는 PLD효소활성은, 암화된 세포에서 더 증가하였으며, control 세포와 core 단백질에 의해 암화된 세포에서 PLD와 PKC 단백질의 발현은 서로 유사하였다. PKC 특이적인 억제제와 PKC의 세포막으로의 이동에 관한 실험을 통해서, PKC-d가 암화된 세포에서 PMA에 의해 유도되는 PLD활성의 증가에 중요하게 관여하고 있음을 밝혔다. 이러한 결과는, PLD가 core 단백질에 의해 유도되는 세포의 암화과정에 관여하고 있을 것으로 추정된다.

Keywords

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