title: Carboxyl-terminus of the amyloid protein precursor and ERbeta are required for estrogenic effect in activating mitogen-activated protein kinase.
abstract: Estrogen influences the processing of the amyloid beta precursor protein (APP) in the pathogenesis of Alzheimer's disease, and this effect is mediated by estrogen receptors (ERs) in activating mitogen-activated protein kinase (MAPK)-signaling pathway. To test whether the estrogenic effect on both carboxyl-terminal amino acid fragment (C-terminal) of APP (APP-C105)- and ERbeta-mediated MAPK activation in in vitro, two hybrid genes containing each human ERbeta and APP-C105 gene fused to the neuron-specific enolase (NSE) promoter were constructed and were transfected to the neuronal SK-N-MC cells. Western blot shows that the activation of JNK-signaling pathway, but not p38 and ERK, is dependent on ERbeta through estrogen treatment and APP-C105 is also mediated through estrogen in activating MAPK-signaling pathway. The results suggest that ERbeta and APP-C105 derived from APP are necessary for estrogenic effect in activating MAPK-signaling pathway.
authors.affiliation: Division of Laboratory Animal Resources, Korea Food and Drug Administration, National Institute of Toxicological Research, Seoul 122-704, Republic of Korea.
authors.forename: Hwa J
authors.initials: HJ
authors.lastname: Lim
authors.forename: Chul J
authors.initials: CJ
authors.lastname: Lim
authors.forename: Dae Y
authors.initials: DY
authors.lastname: Hwang
authors.forename: Su H
authors.initials: SH
authors.lastname: Lee
authors.forename: Sae H
authors.initials: SH
authors.lastname: Min
authors.forename: Youn S
authors.initials: YS
authors.lastname: Song
authors.forename: Su J
authors.initials: SJ
authors.lastname: Seo
authors.forename: Hye K
authors.initials: HK
authors.lastname: Park
authors.forename: Yhun Y
authors.initials: YY
authors.lastname: Sheen
authors.forename: Jung S
authors.initials: JS
authors.lastname: Cho
authors.forename: Yong K
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D014162:Transfection
chemical_list: D016564:Amyloid beta-Protein Precursor; D047629:Estrogen Receptor beta; D004958:Estradiol; D020928:Mitogen-Activated Protein Kinases