Apoptosis-mediated cytotoxicity of prodigiosin-like red pigment produced by γ-Proteobacterium and its multiple bioactivities

Takuji Nakashima*, Tadashi Tamura, Maki Kurachi, Kenichi Yamaguchi, Tatsuya Oda

*この研究の対応する著者

研究成果: Article査読

22 被引用数 (Scopus)

抄録

Recently we discovered a bacterial strain (MS-02-063) that produces large amounts of red pigment (PG-L-1). Among the cell lines tested, U937 cells showed the highest susceptibility to PG-L-1 toxicity. PG-L-1 induced typical apoptotic nuclear morphological changes, and single cell gel electrophoresis revealed that PG-L-1 caused DNA fragmentation in U937 cells. In PG-L-1 treated U937 cells, the acidic compartment such as lysosomes disappeared, suggesting that PG-L-1-induced disorder of intracellular pH compartmentalization might trigger apoptotic signal. Since p38 MAP kinase inhibitor specifically prevented the PG-L-1 mediated cell death, p38 MAP kinase may be involved in the cytotoxic mechanism. In fact, immunoblot analysis of p38 MAP kinase revealed that phosphorylation of p38 MAP kinase occurred in PG-L-1-treated U937 cells. In addition to the activity to induce apoptotic cell death as reported in several PG family members, our chemiluminescence analysis suggested that PG-L-1 inhibited superoxide generation by 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated U937 cells in a dose-dependent manner. Since PG-L-1 had no effect on the chemiluminescence response caused by xanthine oxidase/hypoxanthine system, PG-L-1 acts on the enzyme system responsible for O2 - generation rather than direct scavenging toward O2 -. Our results suggest that PG-L-1 causes multiple biochemical effects on the target cells such as increase in pH in acidic intracellular compartment, activation of p38 MAP kinase, inhibition of O2 - generation, and eventually induces apoptotic cell death.

本文言語English
ページ(範囲)2289-2295
ページ数7
ジャーナルBiological and Pharmaceutical Bulletin
28
12
DOI
出版ステータスPublished - 2005 12
外部発表はい

ASJC Scopus subject areas

  • 薬理学
  • 薬科学

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