タモキシフェンによるアフラトキシンB1誘発ラット肝癌由来K2細胞のアポトーシス誘導過程にはDNase活性を有するヒストンH10断片が関与している

川崎 靖; 安達 尚美; 田村 勇; 米納 孝; 飯田 直幸; 秋山 弘匡; 杉山 晶規; 田代 文夫

doi:10.2520/myco.64.117

Research Paper

Implication of histone H1⁰-derived 17-kDa DNase in tamoxifen-induced apoptosis in aflatoxin B₁-elicited rat hepatocellular carcinoma cells

Yasushi KAWASAKI, Naomi ADACHI, Isamu TAMURA, Takashi KOMENO, Naoyuki IIDA, Hirotada AKIYAMA, Akinori SUGIYAMA, Fumio TASHIRO

Author information

Yasushi KAWASAKI
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science
Department of Health Chemistry, School of Pharmacy, Iwate Medical University
Naomi ADACHI
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science
Isamu TAMURA
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science
Takashi KOMENO
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science
Naoyuki IIDA
Division of Biochemistry, School of Pharmaceutical Science, Kitasato University
Hirotada AKIYAMA
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science
Akinori SUGIYAMA
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science
Department of Health Chemistry, School of Pharmacy, Iwate Medical University
Fumio TASHIRO
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science

Keywords: aflatoxin B₁, apoptosis, DNase, histone H1⁰, tamoxifen

JOURNAL FREE ACCESS

2014 Volume 64 Issue 2 Pages 117-139

DOI https://doi.org/10.2520/myco.64.117

Details

Abstract

The 17-kDa N-terminal region (NTR) of rat histone H1⁰ (Thr 2 - Phe107 ) was generated during TAM-induced apoptosis and acted as a DNase, for which two histidine residues at 25 and 57 were essential. The 17-kDa H1⁰NTR was generated by the restricted cleavage of H1⁰ with the Ca²⁺-dependent protease calpain-2, which was activated by TAM-induced Ca²⁺ influx ([Ca²⁺]_i). The forced expression of the 17-kDa H1⁰NTR stimulated, while its downregulation suppressed TAM-induced apoptosis. These results imply the involvement of the 17-kDa H1⁰NTR DNase downstream of the TAM-triggered cell death signaling pathway, suggest that TAM could be a promising chemoprevention and anticancer drug for AFB₁ hepatocarcinogenesis, and also provide a new insight into the biological functions of H1⁰.

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