Antioxidant enzymes play key roles in the protection of cells from oxidative damage. Little is known, however, about the expression of antioxidants and/or their roles in PMNs (polymorphonuclear leucocytes), which are thought to suffer from oxidative stress in an inflammation site. In the present paper, we report on the regulation of expression of PHGPx (phospholipid hydroperoxide glutathione peroxidase) and cGPx (cytosolic glutathione peroxidase) in rat PMNs in the inflammation site. PHGPx mRNA levels were much lower in casein-induced peritoneal and carrageenan-induced pleural PMNs just after their collection than in peripheral PMNs. cGPx mRNA was also reduced in the casein-induced PMNs, but not in carrageenan-induced PMNs. Both enzymes with decreased levels in the casein-induced PMNs were up-regulated during further 24 h cultivation in vitro and in vivo, with elevation of their protein levels and activities, and reduction of intracellular peroxides. Up-regulation of PHGPx mRNA was attenuated by cycloheximide, a protein synthesis inhibitor, and this effect was cancelled by culturing the cells in the conditioned medium of the cultured casein-induced PMNs. This latter effect was attenuated by pre-treatment with anti-GRO (growth-regulated oncogene) antibody. Recombinant rat GRO could also induce the up-regulation in the presence of cycloheximide, demonstrating that GRO may play an important role in the PHGPx up-regulation of casein-induced PMNs. Production of the lipid mediators leukotriene B4 and 5-HETE (5-hydroxyeicosatetraenoic acid) was decreased in the cultured casein-induced PMNs exhibiting PHGPx up-regulation. The evidence obtained indicates that PHGPx activity in the activated PMNs would be related to the appearance of the intrinsic function of PMNs in the inflammatory site.
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Research Article|
July 05 2005
Up-regulation of phospholipid hydroperoxide glutathione peroxidase in rat casein-induced polymorphonuclear neutrophils
Hiroyuki Hattori;
Hiroyuki Hattori
*School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan
†Drug Safety Research Laboratory, Daiichi Pharmaceutical Co. Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan
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Hirotaka Imai;
Hirotaka Imai
*School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan
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Akiharu Hanamoto;
Akiharu Hanamoto
1
*School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan
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Kazuhisa Furuhama;
Kazuhisa Furuhama
†Drug Safety Research Laboratory, Daiichi Pharmaceutical Co. Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan
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Yasuhito Nakagawa
Yasuhito Nakagawa
2
*School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan
2To whom correspondence should be addressed (email nakagaway@pharm.kitasato-u.ac.jp).
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Publisher: Portland Press Ltd
Received:
January 04 2005
Revision Received:
February 24 2005
Accepted:
March 09 2005
Accepted Manuscript online:
March 09 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 389 (2): 279–287.
Article history
Received:
January 04 2005
Revision Received:
February 24 2005
Accepted:
March 09 2005
Accepted Manuscript online:
March 09 2005
Connected Content
A correction has been published:
Up-regulation of phospholipid hydroperoxide glutathione peroxidase in rat casein-induced polymorphonuclear neutrophils
Citation
Hiroyuki Hattori, Hirotaka Imai, Akiharu Hanamoto, Kazuhisa Furuhama, Yasuhito Nakagawa; Up-regulation of phospholipid hydroperoxide glutathione peroxidase in rat casein-induced polymorphonuclear neutrophils. Biochem J 15 July 2005; 389 (2): 279–287. doi: https://doi.org/10.1042/BJ20050006
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