title: Deletion of microsomal prostaglandin E synthase-1 protects neuronal cells from cytotoxic effects of β-amyloid peptide fragment 31-35.
abstract: Epidemiological studies have suggested that the long-term use of nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase (COX) activity moderates the onset or progression of Alzheimer's disease (AD). Thus it has been suggested that prostaglandin E(2) (PGE(2)), a major end-product of COX, may play a pathogenic role in AD, but the involvement of PGE synthase (PGES), a terminal enzyme downstream from COX, has not been fully elucidated. To examine the involvement in AD pathology of microsomal PGES-1 (mPGES-1), a PGES enzyme, we here prepared primary cerebral neuronal cells from the cerebri of wild-type and mPGES-1-deficient mice and then treated them with β-amyloid (Aβ) fragment 31-35 (Aβ(31-35)), which represents the shortest sequence of native Aβ peptide required for neurotoxicity. Treatment of wild-type neuronal cells with Aβ(31-35) induced mPGES-1 gene expression and PGE(2) production, followed by significant apoptotic cell death, but apoptosis was not induced in mPGES-1-deficient cells. Furthermore, the combined treatment of Aβ(31-35) and PGE(2) induced apoptosis in mPGES-1-deficient neuronal cells. These results indicated that mPGES-1 is induced during Aβ-mediated neuronal cell death and is involved in Aβ-induced neurotoxicity associated with AD pathology.
authors: Department of Health Chemistry, School of Pharmacy, Showa University, Tokyo 142-8555, Japan.
authors: Yukiko
authors: Y
authors: Kuroki
authors: Yuka
authors: Y
authors: Sasaki
authors: Daisuke
authors: D
authors: Kamei
authors: Yoshiharu
authors: Y
authors: Akitake
authors: Mitsuo
authors: M
authors: Takahashi
authors: Satoshi
authors: S
authors: Uematsu
authors: Shizuo
authors: S
authors: Akira
authors: Yoshihito
authors: Y
authors: Nakatani
authors: Ichiro
authors: I
authors: Kudo
authors: Shuntaro
authors: S
authors: Hara
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D017353:Gene Deletion; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D051379:Mice; D008861:Microsomes / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D000071876:Prostaglandin-E Synthases
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse