1994 Fiscal Year Annual Research Report

エストロジェン、癌遺伝子と神経細胞死

Research Project

Project/Area Number	06272106
Research Institution	The Open University of Japan
Principal Investigator	鬼頭昭三放送大学, 教養学部, 教授 (00010140)
Co-Investigator(Kenkyū-buntansha)	福田潤防衛医科大学校, 教授 (50010062) 渡邊康裕防衛医科大学校, 教授 (90127324) 仙波純一放送大学, 教養学部, 助教授 (30183429)
Keywords	カイニン酸 / glucocorticoid / estrogen / in situ hybridization / Ca^<2+> / HGF
Research Abstract	ラット辺縁系培養神経細胞に対してglucocorticoidは、カイニン酸毒性を用量依存性に増加することを認めた。estrogenについては10^<-6>M以下の低濃度では、用量依存的に細胞生存率を増加させる、10^<-5>M以上では、単独で神経細胞生存率を低下させるという結果を得ている。このメカニズムを検討するために、以下の実験を行った。1.estrogenは辺縁系培養神経細胞に対して細胞内Ca^<2+>濃度の上昇をきたし、その持続が通常の伝達物質による数10秒程度の持続のCa^<2+>濃度上昇とは異なって、その持続が10分以上にわたる場合がある。この実験系にN型channel brockerであるω-conotoxineを加えたが、影響がみられなかった。一方、L型channel blockerであるniphedipineを加え、Ca^<2+>濃度上昇の抑制がみられた。このことからこのCa^<2+>濃度上昇の一部はL型channel blockerを介するものであると推定された。また、この実験系にRNA阻害剤としてアクチノマイシンDを加えたところ、部分的にCa^<2+>濃度上昇が抑制された。2.estrogen及び、glucocorticoid投与に伴う辺縁系培養神経細胞における原癌遺伝子発現の有無にについて、in situ hybridizationにより実験を行った。 estrogenの全身投与後30分〜1時間にわたって、海馬、扁桃体などの辺縁系にc-fosおよび、zif286の発現を見ることを認めた。glucocorticoid投与ではこれらの原癌遺伝子発現は見られなかった。このことから、estrogenの低濃度では高濃度の場合とは逆に細胞保護的に働き、そのメカニズムの一つとして、AP-1 siteによって促進的に働くことが考えられる。今後、estrogenとglucococorticoidの同時投与によって原癌遺伝子の発現の有無を見る必要がある。3.肝組織でhepatocyto growth factor(HGF)が神経細胞組織においても修復機転として働くことが推定されている。glucocorticoidによる細胞毒性及び少量のestrogenの細胞保護作用のメカニズムとして原癌遺伝子を介した、HGF mRNAの発現の調節があるものと仮説を立て実験を行った。カイニン酸の全身投与によりラット海馬で投与後6時間から48時間にかけてHGF mRNAが発現することをnothern blotting法により確認した。HGFのreceptorであるc-met mRNAについてもカイニン酸投与後、ほぼ同様な過程で、発現することが知られた。preminaryの結果ではあるが、このカイニン酸によるHGFの発現に対して、estrogenは促進を示しglucocorticoidは抑制を示した。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] Semba,J.: "Behavioral and neurochemical effects of OPC-14597,a novel antipsychotics drugs,on dopaminergic mechanisms in rat brain." Neuropharmacology. (in press).
[Publications] Semba,J.: "Effect of systemic dexamethasone on extracellular amino acids(glutamate,aspartate,glycine and GABA)and acetylcholine release in rat hippocampus in vivo microdialysis." Functional Neurology. (in press).
[Publications] Semba,J.: "Characterisation of extracellular amino acids in striatum of freely moving rats by in vivo microdialysis." J.of Neural Transmission. (in press).
[Publications] Kito,S.: "Effect of nicotine on glucocorticoid toxicity on hippocampal neurons." Neurochemical Research. 19. 888-889 (1994)
[Publications] Kito,S.: "Effects of glucocorticoid on hippocampal neurons:in vivo and in vitro studies." Neurochemical Research. 18. 832
[Publications] Miyoshi,R.: "Effect of caerulein on expression of the immediate early genes,c-fos and zif/268 in the rat brain." Neuroscience Letters. 145. 205-208 (1992)
[Publications] Semba,J.: "Behavioral and neurochemical effects of OPC-14597,a novel antipsychotics drugs,on dopaminergic mechanisms in rat brain." Neuropharmacology. (in press).
[Publications] Semba,J.: "Effect of systemic dexamethasone on extracellular amino acids(glutamate,aspartate,glycine and GABA)and acetylcholine release in rat hippocampus in vivo microdialysis." Functional Neurology. (in press).
[Publications] Semba,J.: "Characterisation of extracellular amino acids in striatum of freely moving rats by in vivo microdialysis." J.of Neural Transmission. (in press).
[Publications] Kito,S.: "Effect of nicotine on glucocorticoid toxicity on hippocampal neurons." Neurochemical Research. 19. 888-889 (1994)
[Publications] Semba,J.: "Antiepileptic drug pharmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid milacemide." Br.J.Pharmacol.108. 1117-1124 (1993)
[Publications] Semba,J.: "Milacemide effects on the temporal interrelationship of amino acids and monoamine metabolites in rat cerebrospinal fluid." European Journal of Pharmacology. 230. 321-326 (1993)
[Publications] Sakuta,H.: "Antiarrhythmic drugs,clofilium andcibenzoline are potent inhibitors of glibenclamide-sensitive K+ currents in Xenopus oocytes." Br.J.Pharmacol.109. 866-872 (1993)
[Publications] Wang,X.B.: "In situ DNA-protein binding:a novel method for detecting DNA-binding activity of transcription factor in brain." Neuroscience Letter. 146. 25-28 (1992)
[Publications] Sakagoshi,N.: "Alterations in the beta-adrenergic receptor system after hypothemic ischemic in hearts with preischemic beta-receptor desensitization." J.Surgical Research. 53. 66-73 (1992)
[Publications] Unchern,S.: "Piperine,a pungent alkaloid,is cytotoxic to cultured neurons from the embryonic rat brain." Biol.Pharm.Bull.17. 403-406 (1994)
[Publications] Suzuki,A.: "Cause of death in 81 autopsied patients with rheumatoid arthritis." J.Rheumatol. 21. 33-36 (1994)
[Publications] Toh,H.: "Incidence and histology of human accessory parotid glands." Anat.Rec.236. 586-590 (1993)

1994 Fiscal Year Annual Research Report

エストロジェン、癌遺伝子と神経細胞死

Principal Investigator

鬼頭 昭三 放送大学, 教養学部, 教授 (00010140)

Research Products

[Publications] Semba,J.: "Behavioral and neurochemical effects of OPC-14597,a novel antipsychotics drugs,on dopaminergic mechanisms in rat brain." Neuropharmacology. (in press).

[Publications] Semba,J.: "Effect of systemic dexamethasone on extracellular amino acids(glutamate,aspartate,glycine and GABA)and acetylcholine release in rat hippocampus in vivo microdialysis." Functional Neurology. (in press).

[Publications] Semba,J.: "Characterisation of extracellular amino acids in striatum of freely moving rats by in vivo microdialysis." J.of Neural Transmission. (in press).

[Publications] Kito,S.: "Effect of nicotine on glucocorticoid toxicity on hippocampal neurons." Neurochemical Research. 19. 888-889 (1994)

[Publications] Kito,S.: "Effects of glucocorticoid on hippocampal neurons:in vivo and in vitro studies." Neurochemical Research. 18. 832

[Publications] Miyoshi,R.: "Effect of caerulein on expression of the immediate early genes,c-fos and zif/268 in the rat brain." Neuroscience Letters. 145. 205-208 (1992)

[Publications] Semba,J.: "Behavioral and neurochemical effects of OPC-14597,a novel antipsychotics drugs,on dopaminergic mechanisms in rat brain." Neuropharmacology. (in press).

[Publications] Semba,J.: "Effect of systemic dexamethasone on extracellular amino acids(glutamate,aspartate,glycine and GABA)and acetylcholine release in rat hippocampus in vivo microdialysis." Functional Neurology. (in press).

[Publications] Semba,J.: "Characterisation of extracellular amino acids in striatum of freely moving rats by in vivo microdialysis." J.of Neural Transmission. (in press).

[Publications] Kito,S.: "Effect of nicotine on glucocorticoid toxicity on hippocampal neurons." Neurochemical Research. 19. 888-889 (1994)

[Publications] Semba,J.: "Antiepileptic drug pharmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid milacemide." Br.J.Pharmacol.108. 1117-1124 (1993)

[Publications] Semba,J.: "Milacemide effects on the temporal interrelationship of amino acids and monoamine metabolites in rat cerebrospinal fluid." European Journal of Pharmacology. 230. 321-326 (1993)

[Publications] Sakuta,H.: "Antiarrhythmic drugs,clofilium andcibenzoline are potent inhibitors of glibenclamide-sensitive K+ currents in Xenopus oocytes." Br.J.Pharmacol.109. 866-872 (1993)

[Publications] Wang,X.B.: "In situ DNA-protein binding:a novel method for detecting DNA-binding activity of transcription factor in brain." Neuroscience Letter. 146. 25-28 (1992)

[Publications] Sakagoshi,N.: "Alterations in the beta-adrenergic receptor system after hypothemic ischemic in hearts with preischemic beta-receptor desensitization." J.Surgical Research. 53. 66-73 (1992)

[Publications] Unchern,S.: "Piperine,a pungent alkaloid,is cytotoxic to cultured neurons from the embryonic rat brain." Biol.Pharm.Bull.17. 403-406 (1994)

[Publications] Suzuki,A.: "Cause of death in 81 autopsied patients with rheumatoid arthritis." J.Rheumatol. 21. 33-36 (1994)

[Publications] Toh,H.: "Incidence and histology of human accessory parotid glands." Anat.Rec.236. 586-590 (1993)

鬼頭昭三放送大学, 教養学部, 教授 (00010140)