title: Ryanodine receptor-mediated interference of neuronal cell differentiation by presenilin 2 mutation.
abstract: Neuronal cell differentiation alterations induced by mutant presenilin 2 (PS2) were investigated in transgenic mice expressing wild-type or mutant-type PS2. Progressive increases in differentiation and marker protein expression were found in neuronal cells expressing wild-type PS2, whereas these processes were much perturbed in mutant-type PS2 with elevated ryanodine-receptor (RyR) expression and intracellular calcium levels. Moreover, dantrolene, a blocker of RyR reduced the PS2 mutation-induced interference of cell differentiation and calcium release, but caffeine, an activator of RyR, exacerbated PS2 mutation-induced interference with cell differentiation. Our results indicate that mutant PS2 inhibits normal neuronal cell differentiation and that RyR-mediated calcium overrelease may be a significant factor.
authors.affiliation: College of Pharmacy, Chungbuk National University, Chungbuk, Korea.
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Lee
authors.forename: Youn Sook
authors.initials: YS
authors.lastname: Song
authors.forename: Dae Youn
authors.initials: DY
authors.lastname: Hwang
authors.forename: Yong Kyu
authors.initials: YK
authors.lastname: Kim
authors.forename: Sang Yun
authors.initials: SY
authors.lastname: Nam
authors.forename: Dae Joong
authors.initials: DJ
authors.lastname: Kim
authors.forename: Young Won
authors.initials: YW
authors.lastname: Yun
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003620:Dantrolene / Q000494:pharmacology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D053766:Presenilin-2; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D013997:Time Factors
chemical_list: D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D016900:Neurofilament Proteins; D010726:Phosphodiesterase Inhibitors; D053766:Presenilin-2; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D003620:Dantrolene; D002118:Calcium