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Publication : Influence of iNOS and COX on peroxiredoxin gene expression in primary macrophages.

First Author  Bast A Year  2010
Journal  Free Radic Biol Med Volume  49
Issue  12 Pages  1881-91
PubMed ID  20869433 Mgi Jnum  J:167094
Mgi Id  MGI:4867147 Doi  10.1016/j.freeradbiomed.2010.09.015
Citation  Bast A, et al. (2010) Influence of iNOS and COX on peroxiredoxin gene expression in primary macrophages. Free Radic Biol Med 49(12):1881-91
abstractText  Peroxiredoxins (Prxs) are a family of multifunctional antioxidant thiol-dependent peroxidases. This study aimed to examine the regulatory mechanisms of Prx gene expression in murine bone marrow-derived macrophages (BMMs) using standardized serum-free conditions. Stimulation with LPS and IFNgamma increased mRNA levels of Prx 1, 2, 4, 5, and 6 in BMMs of both C57BL/6 and BALB/c mice, with Prx 1, 2, 4, and 6 more strongly induced in C57BL/6 BMMs. Further investigations on signaling pathways in C57BL/6 BMMs demonstrated that up-regulation of Prx 5 and 6 by LPS and IFNgamma was associated with the activation of multiple protein kinases, most notably JAK2, PI3K, and p38 MAPK. Our experiments also revealed a contribution of inducible NO synthase-derived nitric oxide to the increase in Prx 1, 2, 4, and 6 mRNA expression, whereas NADPH oxidase-derived superoxide was not involved. Furthermore, we could show that LPS- and IFNgamma-induced gene expression of Prx 6 was also regulated in an NO-independent manner by cyclooxygenases and prostaglandin E(2). Taken together our results indicate a possible role for Prxs in defense mechanisms of activated macrophages against oxidative stress during inflammation or infection.
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