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2002 Fiscal Year Final Research Report Summary

The mechanism of cell death induced by hepatitis B virus X protein

Research Project

Project/Area Number 12672142
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

SHIRAKATA Yumiko  The Cancer Inst., JFCR Dept. Gene Res., 癌研究所・遺伝子研究施設部, 研究員 (60179041)

Co-Investigator(Kenkyū-buntansha) KOIKE Katsuro  The Cancer Inst., JFCR Dept. Gene Res., 癌研究所・遺伝子研究施設部, 部長 (30085625)
Project Period (FY) 2000 – 2002
Keywordshepatitis B virus / X gene / cell death / mitochondria / mitochondrial membrane potential / ROS
Research Abstract

The hepatitis B virus X protein (HBx) has been implicated in the carcinogenicity of this virus as a causative factor by means of its transactivation function in development of hepatocellular carcinoma (HCC). However, we and others have recently reported that HBx is located in mitochondria and causes subsequent cell death. In this study, we therefore examined the mechanism of HBx-related cell death. Using EGFP-fusion constructs of HBx, the region required for its mitochondrial localization was mapped to amino acid (aa) 68 to 117, which is essential for cell death but inactive for transactivation function. In vitro binding analysis supported a notion that the recombinant HBx associates with isolated mitochondria through the region of aa 68 to 117, without causing redistribution of cytochrome c and apoptosis inducing factor (AIF). A cytochemical analysis revealed that mitochondrial membrane potential was decreased by HBx association with mitochondria, suggesting that HBx induces dysfunction of permeability transition pore (PTP) complex. Furthermore, PTP inhibitors, reactive oxygen species (ROS) scavengers and Bcl-x_L, which are known to stabilize mitochondrial membrane potential, prevented HBx-induced cell death. Collectively, the present results suggest that location of HBx in mitochondria of HBV-infected cells causes loss of mitochondtial membrane potential and subsequently induces mitochondria-dependent cell death.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Shirakata, Y., Koike, K: "Hepatitis B virus X protein induces cell death by causing loss of mitochondrial membrane potential"J.Biol.Chem.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小池 克郎: "ウイルス感染"血液・免疫・腫瘍 BIC Forum. 6(2). 25-31 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小池 克郎: "肝炎の遺伝子診断"小児科診療. 64(10). 1487-1491 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小池 克郎: "肝炎ウイルス感染・増殖のメカニズム-----B型肝炎ウイルス増殖のメカニズム-----"Mebio. 20(6). 39-45 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shirakata, Y. and Koike, K: "Hepatitis B virus X protein induces cell death by causing loss of mitochondrial membrane potential."J. Biol. Chem.. in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koike, K.: "Virus infection (in Japanese)"Ketsueki・Men-eki・Syuyou. 6(2). 25-31 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koike, K.: "Genetic diagnosis of hepatitis (in Japanese)"Syounika-shinryou. 64(10). 1487-1491 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koike, K.: "The mechanism of hepatits B virus replication (in Japanese)"Mebio. 20(6). 39-45 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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