title: A peroxovanadium compound induces Xenopus oocyte maturation: inhibition by a neutralizing anti-insulin receptor antibody.
abstract: Synthetic peroxovanadium compounds are a new class of potent inhibitors of protein phosphotyrosine phosphatases. These compounds exhibit insulin-like activity both in vitro and in experimental animals. However, the molecular mechanism by which these compounds exert their biological effect is not well defined. We demonstrate here that several of these compounds induce Xenopus oocyte maturation in vitro, as indicated by germinal vesicle breakdown. Using one of these compounds for further studies, we show that the induction is dose-dependent and is accompanied by activation of maturation promoting factor as well as activation of Xenopus MAP kinase. Like insulin, bpV(pic) causes an acute accumulation of PI(3,4,5)P3 (phosphotidylinositol-3,4,5-trisphosphate), a product of PI 3-kinase. More importantly, bpV(pic)-induced oocyte maturation was abolished by microinjection of a neutralizing monoclonal anti-insulin receptor antibody (17A3) into oocytes or preincubation of oocytes with a PI 3-kinase inhibitor (wortmannin). These results suggest that bpV(pic) acts upstream of the Xenopus IGF-1 receptor in the induction of meiotic maturation, presumably by neutralizing an inhibitory protein tyrosine phosphatase(s) that may regulate the receptor. Finally, using an oocyte-follicle cell complex that responded to human chorionic gonadotropin (hCG) to undergo GVBD, we showed that injection of 17A3 anti-insulin receptor antibody into oocytes did not affect hCG-induced oocyte maturation.
authors.affiliation: Loeb Medical Research Institute, Ottawa Civic Hospital, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Cummings
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.forename: A
authors.initials: A
authors.lastname: Sorisky
authors.forename: X J
authors.initials: XJ
authors.lastname: Liu
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000502:physiology*; D016200:Maturation-Promoting Factor / Q000502:physiology; D008845:Microinjections; D009866:Oogenesis / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors* / Q000276:immunology; D015290:Second Messenger Systems / Q000187:drug effects; D014638:Vanadates / Q000494:pharmacology*; D000077191:Wortmannin; D014982:Xenopus laevis
chemical_list: D000730:Androstadienes; D000911:Antibodies, Monoclonal; D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D006064:Gonadotropins, Equine; D007328:Insulin; D018129:Phosphatidylinositol Phosphates; D010726:Phosphodiesterase Inhibitors; C069276:peroxovanadate; C060974:phosphatidylinositol 3,4,5-triphosphate; D014638:Vanadates; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016200:Maturation-Promoting Factor; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D000077191:Wortmannin