Manganese superoxide dismutase interacts with a large scale of cellular and mitochondrial proteins in low-dose radiation-induced adaptive radioprotection

Angela Eldridge, Ming Fan, Gayle Woloschak, David J. Grdina, Brett A. Chromy, Jian-Jian Li

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The cellular adaptive response to certain low-level genotoxic stresses, including exposure to low-dose ionizing radiation (LDIR), shows promise as a tool to enhance radioprotection in normal cells but not in tumor cells. Manganese superoxide dismutase (MnSOD), a fundamental mitochondrial antioxidant in mammalian cells, plays a key role in the LDIR-induced adaptive response. In this study, we aimed to elucidate the signaling network associated with MnSOD-induced radiation protection. A MnSOD-interacting protein profile was established in LDIR-treated human skin cells. Human skin keratinocytes (HK18) were irradiated with a single dose of LDIR (10 cGy X-ray) and the cell lysates were immunoprecipitated using α-MnSOD and applied to two different gel-based proteomic experiments followed by mass spectrometry for protein identification. Analysis of the profiles of MnSOD-interacting partners before and after LDIR detected various patterns of MnSOD protein-protein interactions in response to LDIR. Interestingly, many of the MnSOD-interacting proteins are known to have functions related to mitochondrial regulation of cell metabolism, apoptosis, and DNA repair. These results provide evidence indicating that in addition to the enzymatic action of detoxifying superoxide, the antioxidant MnSOD may function as a signaling regulator in stress-induced adaptive protection through cell survival pathways.

Original languageEnglish (US)
Pages (from-to)1838-1847
Number of pages10
JournalFree Radical Biology and Medicine
Volume53
Issue number10
DOIs
StatePublished - Nov 15 2012

Keywords

  • Adaptive response
  • Free radicals
  • Human keratinocytes
  • Low-dose radiation
  • MnSOD
  • Protein interaction

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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