title: Prostaglandin E1 protects cultured spinal neurons against the effects of nitric oxide toxicity.
abstract: The effects of prostaglandin (PG) E(1) on NO neurotoxicity were examined using rat cultured spinal neurons. Rat cultured spinal neurons exposed to the NO donor, 2,2'-(hydroxynitrosohydrazono) bis-ethanamine (NOC18), showed neurotoxic effects that were accompanied by apoptotic nuclear change, free radical generation, a reduction in glutathione, and mitochondrial dysfunction. PGE(1), at concentrations of 1-100 nM, protected cultured spinal neurons from NO toxicity by reversing the oxidative and pro-apoptotic properties elicited by NOC18 exposure. The administration of PGE(1) increased the intracellular cyclic AMP (cAMP) levels in cultured spinal neurons. In addition, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis confirmed the existence of EP4, a cAMP-elevating PGE receptor, in cultured spinal neurons. The protective effects of PGE(1) against NO neurotoxicity was partially blocked by an inhibitor of MEK [the mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase], suggesting that the MAPK/ERK pathway may play a significant role in the activity of PGE(1). PGE(1) up-regulated the expression of the anti-apoptotic protein, Bcl-2, as determined by Western blot analysis. PGE(1) also induced the expression of thioredoxin in cultured spinal neurons. Our data indicate that PGE(1) exerts a protective action against NO neurotoxicity in cultured spinal neurons, and suggests a therapeutic potential of PGE(1) against spinal cord disease, such as amyotrophic lateral sclerosis.
authors: Department of Neurology, Hokkaido University School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan. skikuti@med.hokudai.ac.jp
authors: S
authors: S
authors: Kikuchi
authors: K
authors: K
authors: Shinpo
authors: M
authors: M
authors: Niino
authors: S
authors: S
authors: Tsuji
authors: K
authors: K
authors: Iwabuchi
authors: K
authors: K
authors: Onoé
authors: K
authors: K
authors: Tashiro
mesh_terms: D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000633:toxicity*; D020030:Nitric Oxide Donors / Q000633:toxicity; D009603:Nitroso Compounds / Q000633:toxicity; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D013879:Thioredoxins / Q000096:biosynthesis; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D005609:Free Radicals; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013879:Thioredoxins; D000527:Alprostadil; D005978:Glutathione