Sialylation of extracellular superoxide dismutase (EC-SOD) enhances furin-mediated cleavage and secretion

Glycobiology. 2017 Dec 1;27(12):1081-1088. doi: 10.1093/glycob/cwx087.

Abstract

Extracellular superoxide dismutase (EC-SOD, SOD3) protects tissues against oxidative damage by detoxifying superoxide anions, particularly in the lungs and cardiovascular system. EC-SOD undergoes several posttranslational modifications including N-glycosylation and proteolytic cleavage. While the roles of proteolytic cleavage have been well studied, the structure and function of EC-SOD N-glycans are poorly understood. Here we analyzed glycan structures on native EC-SOD purified from human sera, and identified sialylated biantennary structures. Using glycan maturation-defective CHO mutant cells, we further revealed that the presence of terminal sialic acids in the N-glycans of EC-SOD enhanced both the secretion and furin-mediated C-terminal cleavage of EC-SOD. These results provide new insights into how the posttranslational modifications of EC-SOD control its functions.

Keywords: N-glycan; SOD3; extracellular superoxide dismutase (EC-SOD); furin; sialylation.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetulus
  • Furin / genetics
  • Furin / metabolism*
  • Glycosylation
  • Humans
  • N-Acetylneuraminic Acid / genetics
  • N-Acetylneuraminic Acid / metabolism*
  • Protein Processing, Post-Translational / physiology*
  • Proteolysis*
  • Superoxide Dismutase / metabolism*

Substances

  • SOD3 protein, human
  • Superoxide Dismutase
  • FURIN protein, human
  • Furin
  • N-Acetylneuraminic Acid