Mechanisms of Hepatic Apoptosis Induced by D-Galactosamine and its Suppression by Tea-catechin

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Other Title
  • 1. D-Galactosamine誘導肝細胞アポートシスの発生分子機構とTea-catechinによる抑制
  • D-Galactosamine誘導肝細胞アポトーシスの発生分子機構とTea-catechinによる抑制
  • D Galactosamine ユウドウ カン サイボウ アポトーシス ノ ハッセイ ブンシ キコウ ト Tea catechin ニ ヨル ヨクセイ

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Description

A molecular mechanism of hepatocyte apoptosis induced by D-galactosamine (D-GalN) administration was studied. We discovered two novel procaspase-3 activating enzymes, named "lysoapoptases" , located in lysosomes with different molecular weights of 52kDa and 18kDa. The content of 52kDa lysoapoptase (lysoapoptase-52) in lysosomes was altered by D-GalN administration. Only the lysoapoptase-52 was released dose-dependently into the cytoplasm by the treatment, while 18kDa-lysoapoptase was kept constant in the lysosomes. As the results, lysoapoptase-52 in the cytoplasm increased quantitatively and activated procaspase-3 to the active caspase-3 in the cytoplasm, which in turn induced hepatocyte apoptosis and also elevation of the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) . When tea-catechin was administred with D-GalN, the lysoapoptase-52 release into the cytoplasm was suppressed significantly. As the result, the active caspase-3 in the cytoplasm was decreased and the serum AST and ALT activities were also not elevated. However, treatment of CA-074 or E-64 could not protected these phenomena.

Journal

  • VITAMINS

    VITAMINS 76 (5-6), 283-289, 2002

    THE VITAMIN SOCIETY OF JAPAN

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