Skip Navigation



Journal of Biochemistry Advance Access published online on October 27, 2007
Journal of Biochemistry, doi:10.1093/jb/mvm196
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow All Versions of this Article:
143/1/107    most recent
mvm196v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Nakashima, T.
Right arrow Articles by Oda, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakashima, T.
Right arrow Articles by Oda, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 The Japanese Biochemical Society

A prodigiosin analogue inactivates NADPH oxidase in macrophage cells by inhibiting assembly of p47phox and Rac

Takuji Nakashima1,2, Takashi Iwashita3, Tsuyoshi Fujita3, Emiko Sato4, Yoshimi Niwano4, Masahiro Kohno4, Shunsuke Kuwahara5, Nobuyuki Harada5, Satoshi Takeshita6 and Tatsuya Oda2

1NITE Biological Resource Center (NBRC), National Institute of Technology and Evaluation (NITE), Japan, 2Division of Biochemistry, Faculty of Fisheries, Nagasaki University, Japan, 3Institute for Bioorganic Research, Suntory, Japan, 4New Industry Creation Hatchery Center, Tohoku University, Japan, 5Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Japan, and 6Joint Research Center, Nagasaki University, Japan

Correspondence to: Dr. Takuji Nakashima, Ph. D. 2-5-8, Kazusakamatari, Kisarazu-shi, Chiba 292-0812, Japan. Tel: +81-438-20-5764; Fax: +81-438-52-2314; E-mail: nakashima-takuji{at}nite.go.jp

Received August 6, 2007; Accepted October 9, 2007


  Abstract

Summary: Prodigiosins are natural red pigments that have multi-biological activities. Recently, we discovered a marine bacterial strain, which produces a red pigment. Extensive two-dimensional nuclear magnetic resonance and mass spectrometry analysis showed that the pigment is a prodigiosin analogue (PG-L-1). Here, we investigated the effect of PG-L-1 on NADPH oxidase activity in macrophage cells. PG-L-1 significantly inhibited superoxide anion (O2-) production by phorbol 12-myristate 13-acetate (PMA)-stimulated RAW264.7 cells, a mouse macrophage cell line. The ED50 value was estimated to be approximately 0.3 µM. PG-L-1 had no direct scavenging effect on O2- generated by hypoxanthine/xanthine oxidase system in electron spin resonance-spin trapping determinations, suggesting that this compound directly acts on the O2- production system, NADPH oxidase, in macrophage cells. We further investigated the effect of PG-L-1 on the behavior of the cytosolic components of the NADPH oxidase, p67phox, p47phox, p40phox, Rac and protein kinas C (PKC), in PMA-stimulated RAW264.7 cells. Although PG-L-1 showed no effect on the activation of PKC, the immunoblotting analysis using specific antibodies showed that PG-L-1 strongly inhibits the association of p47phox and Rac in the plasma membrane of PMA-stimulated RAW264.7 cells. These results suggest that PG-L-1 inactivates NADPH oxidase through the inhibition of the binding of p47phox and Rac to the membrane components of NADPH oxidase.

Key Words: NADPH oxidase inhibitor, prodigiosin, p47phox, Rac protein, superoxide


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 MicrobiologyHome page
K. E. Keith, D. W. Hynes, J. E. Sholdice, and M. A. Valvano
Delayed association of the NADPH oxidase complex with macrophage vacuoles containing the opportunistic pathogen Burkholderia cenocepacia
Microbiology, April 1, 2009; 155(4): 1004 - 1015.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.