title: Nitric oxide induces prion protein via MEK and p38 MAPK signaling.
abstract: The prion diseases or transmissible spongiform encephalopathy, such as human Creutzfeldt-Jakob disease (CJD) and so-called mad cow disease, are attributed to the causative agent, the scrapie variant of prion protein (PrP(Sc)) which causes fatal neurodegeneration. To investigate if stresses such as nitric oxide (NO) induced the cellular isoform of prion protein (PrP(C)), lipopolysaccharide, and sodium nitroprusside were used to treat N2a and NT2 cells, which resulted in elevated levels of the PRNP mRNA and prion protein. The signaling pathway for the NO-induced PrP(C) production involved guanylyl cyclase, MEK, and p38 MAPK as shown by the effect of specific pharmacological inhibitors ODQ, PD98059, and SB203580, respectively. Knowing the PrP induction by the biologically existing stimulus, this study provides useful information about the possible cellular mechanism and strategies for the treatment of CJD.
authors.affiliation: Department of Neurology, Cardinal Tien Hospital, Taipei, Taiwan, ROC.
authors.forename: Vinchi
authors.initials: V
authors.lastname: Wang
authors.forename: Tzu-Chao
authors.initials: TC
authors.lastname: Chuang
authors.forename: Yaw-Don
authors.initials: YD
authors.lastname: Hsu
authors.forename: Wei-Yuan
authors.initials: WY
authors.lastname: Chou
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Kao
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D018620:PrPSc Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D018620:PrPSc Proteins; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D006162:Guanylate Cyclase