Ryanodine receptor-mediated interference of neuronal cell differentiation by presenilin 2 mutation.
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.
Lee
Sang Min
SM
College of Pharmacy, Chungbuk National University, Chungbuk, Korea.
Lee
Jae Woong
JW
Song
Youn Sook
YS
Hwang
Dae Youn
DY
Kim
Yong Kyu
YK
Nam
Sang Yun
SY
Kim
Dae Joong
DJ
Yun
Young Won
YW
Yoon
Do Young
DY
Hong
Jin Tae
JT
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
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