Plasminogen activator inhibitor-1 aids survival of neurites on neurons derived from pheochromocytoma (PC-12) cells.
Plasminogen activator inhibitor-1 is a serpin that regulates the activities of plasminogen activators. However, its physiological roles in the CNS are incompletely understood. We have found that plasminogen activator inhibitor-1 has a novel biological function in the CNS: the contribution to survival of neurites on neurons. PC-12 cells treated with nerve growth factor differentiated into neurons and formed a network of neurites. In a serum-free culture medium, these neurites disappeared within 24 h. The addition of plasminogen activator inhibitor-1 prevented the disintegration of the neuronal networks, while the addition of the serpin inhibitors aprotinin and antipain did not. The plasminogen activator inhibitor-1 maintained or promoted the phosphorylated state of extracellular signal-regulated kinase (ERK), but not of protein kinase B (Akt). These results are the first evidence that plasminogen activator inhibitor-1 in the CNS acts to maintain the morphology of neurites via activation of the ERK-related pathway in the neurons.
Soeda
Shinji
S
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Imatoh
Takuya
T
Ochiai
Takashi
T
Koyanagi
Satoru
S
Shimeno
Hiroshi
H
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015850:Interleukin-6 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D016716:PC12 Cells; D010673:Pheochromocytoma; D010766:Phosphorylation / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000494:pharmacology*; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D020932:Nerve Growth Factor; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases