Heat-shock protein 25 (Hspb1) regulates manganese superoxide dismutase through activation of Nfkb (NF-κB)

Min Jeong Yi, Sang Hee Park, Hye Nyun Cho, Hee Yong Chung, Jong Il Kim, Chul Koo Cho, Su Jae Lee, Yun Sil Lee

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27 Scopus citations

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 (Illb) genes was examined. Increased expression of Tnf and Illb 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-kBα (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 Illb and facilitated SOD2 gene expression through Nfkb activation, possibly resulting in Hspb1-mediated radioresistance.

Original languageEnglish
Pages (from-to)641-649
Number of pages9
JournalRadiation Research
Volume158
Issue number5
DOIs
StatePublished - 1 Nov 2002

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