title: Long-term treatment of anterior pituitary cells with nitric oxide induces programmed cell death.
abstract: Nitric oxide (NO) plays a complex role in modulating programmed cell death. It can either protect the cell from apoptotic death or mediate apoptosis, depending on its concentration and the cell type and/or status. In this study, we demonstrate that long-term exposition to NO induces cell death of anterior pituitary cells from Wistar female rats. DETA NONOate (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, 1 mm], a NO donor that releases NO for an extended period of time, decreased cellular viability and prolactin release from primary cultures of anterior pituitary cells. Morphological studies showed an increase in the number of cells with chromatin condensation and nuclear fragmentation at 24 and 48 h after DETA/NO exposure. DNA internucleosomal fragmentation was also observed at the same time. Reversibility of the NO effect on cellular viability and prolactin release was observed only when the cells were incubated with DETA/NO for less than 6 h. Most apoptotic cells were immunopositive for prolactin, suggesting a high susceptibility of lactotrophs to the effect of NO. The cytotoxic effect of NO is dependent of caspase-9 and caspase-3, but seems to be independent of oxidative stress or nitrosative stress. Our results show that the exposition of anterior pituitary cells to NO for long periods induces programmed cell death of anterior pituitary cells.
authors.affiliation: Centro de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: Miguel Omar
authors.initials: MO
authors.lastname: Velardez
authors.forename: Ariel Hernán
authors.initials: AH
authors.lastname: Poliandri
authors.forename: Jimena Paula
authors.initials: JP
authors.lastname: Cabilla
authors.forename: Cristian Carlos Armando
authors.initials: CC
authors.lastname: Bodo
authors.forename: Leticia Inés
authors.initials: LI
authors.lastname: Machiavelli
authors.forename: Beatriz Haydeé
authors.initials: BH
authors.lastname: Duvilanski
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D005260:Female; D009569:Nitric Oxide / Q000008:administration & dosage*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; D011388:Prolactin