Platelet-activating factor enhances the expression of nerve growth factor in normal human astrocytes under hypoxia.
Nerve growth factor (NGF) is required for the survival of neurons. We have addressed the effect of platelet-activating factor (PAF), one of the mediators of ischemic injury of the brain, on NGF expression in astrocytes. Normal human astrocytes in culture were stimulated with PAF, and levels of NGF mRNA and protein were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA). PAF increased the expressions of NGF mRNA and protein in astrocytes in time- and concentration-dependent manners. After 48-h stimulation, 10 nmol/L PAF increased the levels of NGF protein in astrocyte-conditioned medium by 1.4-fold. The PAF-induced stimulation of NGF expression was further enhanced (2.1-fold of the control) in the cells under hypoxic culture condition. BN52021 (Ginkgolide B), an antagonist for PAF binding sites, suppressed the effect of PAF. We conclude that PAF enhances NGF gene expression in human astrocytes, and the PAF-induced increase in the expression of NGF under hypoxia may benefit the protection of the nervous tissue by promoting neuronal survival.
Yoshida
Hidemi
H
Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. hidemiyo@cc.hirosaki-u.ac.jp
Imaizumi
Tadaatsu
T
Tanji
Kunikazu
K
Sakaki
Hirotaka
H
Metoki
Norifumi
N
Hatakeyama
Masaharu
M
Yamashita
Koji
K
Ishikawa
Akira
A
Taima
Kageaki
K
Sato
Yoshihiro
Y
Kimura
Hiroto
H
Satoh
Kei
K
D001253:Astrocytes / Q000187:drug effects*; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D046934:Ginkgolides; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D004224:Diterpenes; D046934:Ginkgolides; D005904:Glial Fibrillary Acidic Protein; D007502:Iron Chelating Agents; D007783:Lactones; D009414:Nerve Growth Factors; D010972:Platelet Activating Factor; D012333:RNA, Messenger; C045856:ginkgolide B; D003676:Deferoxamine