Immunosuppressant FK506 induces sustained activation of MAP kinase and promotes neurite outgrowth in PC12 mutant cells incapable of differentiating.
During the continuous culturing of neural PC12 cells, a drug hypersensitive PC12 mutant cell line (PC12m3) was obtained, which demonstrated high neurite outgrowth when stimulated by various drugs. When the immunosuppressant drug FK506 and nerve growth factor (NGF) were introduced to the PC12m3 cells, the frequency of neurite outgrowth increased approximately 40-fold for NGF alone. However, the effect of FK506 on neuritogenesis in PC12 parental and drug insensitive PC12m1 mutant cells was much lower than in PC12m3 cells. The sustained activation of mitogen-activated protein (MAP) kinase plays an important role in neurite outgrowth of PC12 cells. Interestingly, the drug hypersensitive PC12m3 cells exhibited the sustained activation of MAP kinase with FK506 in comparison to low or no activities in PC12 parental or drug insensitive PC12m1 cells. These results indicate that PC12m3 cells have a novel FK506-induced MAP kinase pathway for neuritogenesis.
Kano
Yoshio
Y
Department of Occupational Therapy, Kibi International University, Okayama, Japan. yoshio@kiui.ac.jp
Hiragami
Fukumi
F
Kawamura
Kenji
K
Kimata
Yuko
Y
Nakagiri
Sachiko
S
Poffenberger
Chikako K
CK
Akiyama
Junichi
J
Okishima
Kyota
K
Koike
Yoshihisa
Y
Gomita
Yutaka
Y
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D048429:Cell Size / Q000187:drug effects / Q000235:genetics; D004347:Drug Interactions / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D009154:Mutation / Q000187:drug effects / Q000502:physiology; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D018631:ras Proteins / Q000187:drug effects / Q000378:metabolism
D007166:Immunosuppressive Agents; D020932:Nerve Growth Factor; D018631:ras Proteins; D016559:Tacrolimus