TY - JOUR
T1 - Cu,Zn superoxide dismutase increases intracellular calcium levels via a phospholipase C-protein kinase C pathway in SK-N-BE neuroblastoma cells
AU - Mondola, Paolo
AU - Santillo, Mariarosaria
AU - Serù, Rosalba
AU - Damiano, Simona
AU - Alvino, Claudio
AU - Ruggiero, Giuseppina
AU - Formisano, Pietro
AU - Terrazzano, Giuseppe
AU - Secondo, Agnese
AU - Annunziato, Lucio
PY - 2004/11/12
Y1 - 2004/11/12
N2 - 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.
AB - 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.
KW - Antioxidants
KW - Calcium
KW - Intracellular signalling
KW - SOD1
UR - http://www.scopus.com/inward/record.url?scp=5144226540&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=5144226540&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2004.09.131
DO - 10.1016/j.bbrc.2004.09.131
M3 - Article
C2 - 15474511
AN - SCOPUS:5144226540
VL - 324
SP - 887
EP - 892
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -