Oxidative modifications of S100 proteins: Functional regulation by redox

Yin Lim Su, Mark J. Raftery, Jesse Goyette, Kenneth Hsu, Carolyn L. Geczy

Research output: Contribution to journalReview articlepeer-review

105 Citations (Scopus)

Abstract

Several S100 Ca2+-binding proteins undergo various post-translational modifications that may alter their intracellular and extracellular functions. S100A8 and S100A9, two members of this family, are particularly susceptible to oxidative modification. These proteins, abundantly expressed in neutrophils and activated macrophages, are associated with acute and chronic inflammatory conditions, including microbial infections, cystic fibrosis, rheumatoid arthritis, and atherosclerosis. They have diverse intracellular roles including NADPH oxidase activation and arachidonic acid transport and can be secreted via a Golgi-independent pathway to exert extracellular functions. Many pro-inflammatory functions have been described for S100A8 and S100A9, but they are also implicated in anti-inflammatory roles in wound-healing and protection against excessive oxidative tissue damage, the latter as a result of their exquisite capacity to scavenge oxidants. Similarly, their genes are induced by proinflammatory (LPS and TNF-α) stimuli, but induction is IL-10-dependent, and anti-inflammatory glucocorticoids induce or amplify expression. S100A8 and S100A9 were described recently as damage-associated molecular pattern molecules, which provide a novel, conceptual framework for understanding their functions. However, because of this designation, recent reviews focus solely on their pro-inflammatory functions. Here, we summarize the mounting evidence from functional and gene regulation studies that these proteins may also play protective roles. This review offers an explanation for the disparate, functional roles of S100A8 and S100A9 based on emerging data that post-translational, oxidative modifications may act as a regulatory switch.

Original languageEnglish
Pages (from-to)577-587
Number of pages11
JournalJournal of Leukocyte Biology
Volume86
Issue number3
DOIs
Publication statusPublished - 1 Sep 2009
Externally publishedYes

Keywords

  • Calgranulins
  • Gene regulation
  • Mass spectrometry
  • Oxidation
  • Post-translational modifications
  • S100A8/A9

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