title: Activation of MAPK by potassium bisperoxo(1,10-phenanthroline)oxovanadate (V).
abstract: Potassium bisperoxo(1,10-phenantroline)oxovanadate (V) [bpV(phen)] is a potent protein tyrocine phosphatase inhibitor which mediates a variety of biological effects. The aim of these studies was to examine the role(s) of mitogen activated protein kinase (MAPK) pathways in PC12 cell proliferation and toxicity by bpV(phen). BpV(phen) exerts a bimodal effect in PC12 cells: proliferation at low and cell death at higher micromolar concentrations. Activation of MAPK by bpV(phen) depends on time and concentration. The phosphorylation pattern of extracellular regulated kinases (ERK 1/2), c-jun N-terminal activated kinases (JNK) and p38 in PC12 cells is strikingly different. Activation of JNK is sustained in PC12 cells. In contrast, ERK 1/2 activation is transient and treatment with PD98059 indicates that ERK activation by bpV(phen) is partly independent from the ras-MEK pathway. Stability studies of bpV(phen) in DMEM and PBS showed linear relationship with T1/2 about 6 h and 10 days in DMEM and PBS, respectively. Comparison between the time courses of MAPK activation and kinetics of bpV(phen) decomposition as assessed by 51V-NMR analysis show that the initial and maximal phosphorylation signals are produced in the presence of the complex bpV(phen) and not caused by the decomposition products of bpV(phen).
authors.affiliation: Department of Molecular Biology, Faculty of Science, University of Zagreb, Croatia.
authors.forename: Z
authors.initials: Z
authors.lastname: Cerovac
authors.forename: J
authors.initials: J
authors.lastname: Ban
authors.forename: A
authors.initials: A
authors.lastname: Morinville
authors.forename: K
authors.initials: K
authors.lastname: Yaccato
authors.forename: A
authors.initials: A
authors.lastname: Shaver
authors.forename: D
authors.initials: D
authors.lastname: Maysinger
mesh_terms: D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009942:Organometallic Compounds / Q000494:pharmacology*; D016716:PC12 Cells; D010618:Phenanthrolines / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D009942:Organometallic Compounds; D010618:Phenanthrolines; C102120:bisperoxo(1,10-phenanthroline)oxovanadate(1-); D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases