title: nNOS is involved in estrogen mediated neuroprotection in neuroblastoma cells.
abstract: Estrogens exert neuroprotective activity in both in vivo and in vitro model systems. Herein, we report that both 17beta-estradiol and low concentrations of nitric oxide (NO) attenuate hydrogen peroxide (H2O2) induced toxicity in SK-N-SH cells, which express the neuronal nitric oxide synthase (nNOS). 17beta-estradiol rapidly induced an increase in NO levels. A nNOS inhibitor was able to block the neuroprotection of 17beta-estradiol. Cyclic guanylyl mono-phosphate (cGMP) also protected against H2O2 induced toxicity, while NO's protection was attenuated by ODQ, a soluble guanylyl cyclase (sGC) inhibitor. In SK-N-SH cells, the major estrogen receptor isoforms is estrogen receptor beta. Our current study suggests that increased activity of nNOS may be involved in the neuroprotection conferred by 17beta-estradiol.
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107l, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wen
authors.forename: Evelyn J
authors.initials: EJ
authors.lastname: Perez
authors.forename: Pattie S
authors.initials: PS
authors.lastname: Green
authors.forename: Saumyendra N
authors.initials: SN
authors.lastname: Sarkar
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
mesh_terms: D045744:Cell Line, Tumor; D006152:Cyclic GMP / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009603:Nitroso Compounds / Q000494:pharmacology; D016877:Oxidants / Q000633:toxicity
chemical_list: C093285:NOC 18; D018696:Neuroprotective Agents; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D016877:Oxidants; D009569:Nitric Oxide; D004958:Estradiol; D006861:Hydrogen Peroxide; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D006152:Cyclic GMP