[A novel function of anti-fibrinolytic factor, PAI-1, in the central nervous system: a possible role as the neurotrophic factor].
Plasminogen activator inhibitor-1 (PAI-1) is a serpin that suppresses fibrinolysis by inhibiting the activity of plasminogen activator (PA). Together with PA, PAI-1 is expressed in the central nervous system and may play a role in the regulation of PA activity. Our present study has demonstrated that, in cultures of PC-12 neurons, depletion of PAI-1 from the culture medium induces disappearance of the cell's neurites and the cell death. Aprotinin and antipain, the inhibitors of PA, were not counterparts of PAI-1 in the protection of neurite disappearance. We also found that PAI-1 had the abilities to promote release of the survival factors of neurons, IL-6 and VEGF and activation of a survival serine/threonine kinase Akt. These results suggest that PAI-1 has physiological functions other than its role as PA inhibitor for the survival of neurons.
Imatoh
Takuya
T
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
Soeda
Shinji
S
Ochiai
Takashi
T
Shimeno
Hiroshi
H
D000818:Animals; D001921:Brain / Q000502:physiology*; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000494:pharmacology / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D008222:Lymphokines; D009414:Nerve Growth Factors; D017395:Plasminogen Activator Inhibitor 1; D011518:Proto-Oncogene Proteins; D015842:Serine Proteinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt