Cu,Zn superoxide dismutase increases intracellular calcium levels via a phospholipase C-protein kinase C pathway in SK-N-BE neuroblastoma cells

Paolo Mondola, Mariarosaria Santillo, Rosalba Serù, Simona Damiano, Claudio Alvino, Giuseppina Ruggiero, Pietro Formisano, Giuseppe Terrazzano, Agnese Secondo, Lucio Annunziato

Research output: Contribution to journalArticlepeer-review

Abstract

The superoxide dismutase isoenzymes (SOD) play a key role in scavenging, O 2 .- radicals. In contrast with previous studies, recent data have shown that human neuroblastoma cells are able to export the cytosolic Cu,Zn superoxide dismutase (SOD1), thus suggesting a paracrine role exerted by this enzyme in the nervous system. To evaluate whether SOD1 could activate intracellular signalling pathways, the functional interaction between SOD1 and human neuroblastoma SK-N-BE cells was investigated. By analyzing the surface binding of biotinylated SOD1 on SK-N-BE cells and by measuring intracellular calcium concentrations and PKC activity, we demonstrated that SOD1 specifically interacts in a dose-dependent manner with the cell surface membrane of SK-N-BE. This binding was able to activate a PLC-PKC-dependent pathway that increased intracellular calcium concentrations mainly deriving from the intracellular stores. Furthermore, we showed that this effect was independent of SOD1 dismutase activity and was totally inhibited by U73122, the PLC blocker. On the whole, these data indicate that SOD1 carries out a neuromodulatory role affecting calcium-dependent cellular functions.

Original languageEnglish
Pages (from-to)887-892
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume324
Issue number2
DOIs
Publication statusPublished - Nov 12 2004

Keywords

  • Antioxidants
  • Calcium
  • Intracellular signalling
  • SOD1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Fingerprint Dive into the research topics of 'Cu,Zn superoxide dismutase increases intracellular calcium levels via a phospholipase C-protein kinase C pathway in SK-N-BE neuroblastoma cells'. Together they form a unique fingerprint.

Cite this