title: The Cu-Zn superoxide dismutase (SOD1) inhibits ERK phosphorylation by muscarinic receptor modulation in rat pituitary GH3 cells.
abstract: The Cu-Zn superoxide dismutase (SOD1) belongs to a family of isoenzymes that are able to dismutate the oxygen superoxide in hydrogen peroxide and molecular oxygen. This enzyme is secreted by many cellular lines and it is also released trough a calcium-dependent depolarization mechanism involving SNARE protein SNAP 25. Using rat pituitary GH3 cells that express muscarinic receptors we found that SOD1 inhibits P-ERK1/2 pathway trough an interaction with muscarinic M1 receptor. This effect is strengthened by oxotremorine, a muscarinic M agonist and partially reverted by pyrenzepine, an antagonist of M1 receptor; moreover this effect is independent from increased intracellular calcium concentration induced by SOD1. Finally, P-ERK1/2 inhibition was accompanied by the reduction of GH3 cell proliferation. These data indicate that SOD1 beside the well studied antioxidant properties can be considered as a neuromodulator able to affect mitogen-activated protein kinase in rat pituitary cells trough a M1 muscarinic receptor.
authors.affiliation: Department of Neuroscience, Section of Pharmacology, University of Naples "Federico II", Via S. Pansini, 5, 80131 Naples, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Secondo
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: De Mizio
authors.forename: Laura
authors.initials: L
authors.lastname: Zirpoli
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Santillo
authors.forename: Paolo
authors.initials: P
authors.lastname: Mondola