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Apoptosis-Mediated Cytotoxicity of Prodigiosin-Like Red Pigment Produced by γ-Proteobacterium and Its Multiple Bioactivities

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Title: Apoptosis-Mediated Cytotoxicity of Prodigiosin-Like Red Pigment Produced by γ-Proteobacterium and Its Multiple Bioactivities
Authors: Nakashima, Takuji / Tamura, Tadashi / Kurachi, Maki / Yamaguchi, Kenichi / Oda, Tatsuya
Issue Date: Dec-2005
Publisher: Pharmaceutical Society of Japan.
Citation: Biological & Pharmaceutical Bulletin v.28(12) p.2289-2295, 2005
Abstract: 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 O_2- generation rather than direct scavenging toward O_2-. 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 O_2- generation, and eventually induces apoptotic cell death.
Keywords: prodigiosin / apoptosis / superoxide / U937 cell / γ-proteobacterium
URI: http://hdl.handle.net/10069/8333
ISSN: 09186158
DOI: 10.1248/bpb.28.2289
PubMed ID: 16327167
Relational Links: http://dx.doi.org/10.1248/bpb.28.2289
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/8333

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