title: Inhibition of germinal vesicle breakdown by antioxidants and the roles of signaling pathways related to nitric oxide and cGMP during meiotic resumption in oocytes of a marine worm.
abstract: In mammalian oocytes, cAMP elevations prevent the resumption of meiotic maturation and thereby block nuclear disassembly (germinal vesicle breakdown (GVBD)), whereas nitric oxide (NO) and its downstream mediator cGMP can either inhibit or induce GVBD. Alternatively, some invertebrate oocytes use cAMP to stimulate, rather than inhibit, GVBD, and in such cases, the effects of NO/cGMP signaling on GVBD remain unknown. Moreover, potential interactions between NO/cGMP and AMP-activated kinase (AMPK) have not been assessed during GVBD. Thus, this study analyzed intraoocytic signaling pathways related to NO/cGMP in a marine nemertean worm that uses cAMP to induce GVBD. For such tests, follicle-free nemertean oocytes were stimulated to mature by seawater (SW) and cAMP elevators. Based on immunoblots and NO assays of maturing oocytes, SW triggered AMPK deactivation, NO synthase (NOS) phosphorylation, and an NO elevation. Accordingly, SW-induced GVBD was blocked by treatments involving the AMPK agonist AICAR, antioxidants, the NO scavenger carboxy-PTIO, NOS inhibitors, and cGMP antagonists that target the NO-stimulated enzyme, soluble guanylate cyclase (sGC). Conversely, SW solutions combining NO/cGMP antagonists with a cAMP elevator restored GVBD. Similarly, AICAR plus a cAMP-elevating drug reestablished GVBD while deactivating AMPK and phosphorylating NOS. Furthermore, sGC stimulators and 8-Br-cGMP triggered GVBD. Such novel results indicate that NO/cGMP signaling can upregulate SW-induced GVBD and that cAMP-elevating drugs restore GVBD by overriding the inhibition of various NO/cGMP downregulators, including AMPK. Moreover, considering the opposite effects of intraoocytic cAMP in nemerteans vs mammals, these data coincide with previous reports that NO/cGMP signaling blocks GVBD in rats.
authors.affiliation: Department of Biology, University of New Mexico, Albuquerque, New Mexico 87131, USA. sstr@unm.edu
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Stricker
mesh_terms: D000818:Animals; D000845:Annelida / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000975:Antioxidants / Q000494:pharmacology*; D059001:Aquatic Organisms / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D054239:Blastodisc / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D008540:Meiosis / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009866:Oogenesis / Q000187:drug effects; D051381:Rats; D012623:Seawater; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000975:Antioxidants; D009569:Nitric Oxide; D006152:Cyclic GMP