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PMID:12385642

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Citation

Yi, MJ, Park, SH, Cho, HN, Yong Chung, H, Kim, JI, Cho, CK, Lee, SJ and Lee, YS (2002) Heat-shock protein 25 (Hspb1) regulates manganese superoxide dismutase through activation of Nfkb (NF-kappaB). Radiat. Res. 158:641-9

Abstract

We previously demonstrated that overexpression of HSP25 (now known as Hspb1) conferred increased resistance to ionizing radiation (Radiat Res. 154, 421-428, 2000). In the present study, L929 cells overexpressing Hspb1 were shown to have increased expression of the manganese superoxide dismutase gene (now known as SOD2) and its enzyme activity. To elucidate Hspb1-induced pathways leading to activation of these antioxidant enzymes, the production of the tumor necrosis factor alpha (Tnf) and interleukin 1 beta (Il1b) genes was examined. Increased expression of Tnf and Il1b resulting from Hspb1 overexpression was detected by RT-PCR. Increased activation of Nfkb (degradation of Ikb, a member of the Nfkb family) was also found in Hspb1-overexpressing cells. When treated with Tnf, Nfkb activation and SOD2 gene expression were increased more by Hspb1 overexpression. Moreover, transfection with the Hspb1 antisense gene abrogated all of the Hspb1-mediated phenomena. To further elucidate the exact relationship between induction of SOD2 and Nfkb activation, a dominant negative I-kBalpha (now known as Nfkb1a) construct was transfected into Hspb1-overexpressing cells. The dominant negative Nfkb1a inhibited Hspb1-mediated SOD2 gene expression. In addition, Hspb1-mediated radioresistance was blocked by dominant negative Nfkb1a transfection. When the SOD2 gene was transfected into L929 cells, a somewhat increased radioresistance was detected by a clonogenic survival assay compared to control cells. Hspb1 produced Tnf and Il1b and facilitated SOD2 gene expression through Nfkb activation, possibly resulting in Hspb1-mediated radioresistance.

Links

PubMed

Keywords

Animals; Blotting, Western; Cell Line; Dose-Response Relationship, Radiation; Gamma Rays/adverse effects; Gene Expression Regulation/radiation effects; Heat-Shock Proteins; Interleukin-1/genetics; Interleukin-1/metabolism; Mice; NF-kappa B/genetics; NF-kappa B/metabolism; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; RNA, Messenger/genetics; RNA, Messenger/metabolism; Radiation Tolerance/genetics; Reverse Transcriptase Polymerase Chain Reaction; Superoxide Dismutase/genetics; Superoxide Dismutase/metabolism; Transfection; Tumor Necrosis Factor-alpha/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:HSPB1

involved_in

GO:0032760: positive regulation of tumor necrosis factor production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HSPB1

involved_in

GO:0032731: positive regulation of interleukin-1 beta production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HSPB1

involved_in

GO:0043122: regulation of I-kappaB kinase/NF-kappaB signaling

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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