1998 Fiscal Year Annual Research Report

アポトーシスにおける新規情報変換酵素ホスホリパーゼD(PLD)の役割

Research Project

Project/Area Number	10670136
Research Institution	Gifu University
Principal Investigator	中島茂岐阜大学, 医学部, 助教授 (60188935)
Co-Investigator(Kenkyū-buntansha)	坂野喜子岐阜大学, 医学部, 講師 (50116852)
Keywords	ホスホリパーゼD / アポトーシス / 細胞分化 / チロシンキナーゼ / MAPキナーゼ / 酵素ストレス
Research Abstract	アポトーシスでは膜リン脂質スフィンゴミエリン(SM)のスフィンゴミエリナーゼ(SMアーゼ)による分解産物セラミドが重要な細胞内メッセンジャーとして位置づけられつつある。一方、情報変換酵素ホスホリパーゼD(PLD)は分泌応答などの迅速応答から、細胞の増殖・分化といった中長期的応答にまで関与することから注目を集めている。アルツハイマー病患者脳では著しいPLD活性の低下が示されており、細胞の機能維持にPLDの重要性が示唆されている。C6細胞ではC2セラミドによりアポトーシスが誘導されるが、その際にはG蛋白質依存性のPLD活性とrPLD1aおよびrPLD1bmRNAの著明な減少が見られた。同様の変化は、他の細胞系(RBL、PC12、HaCatなど)および他のアポトーシス誘導因子であるTNF-αとH_2O_2でも認められた。従って、セラミド系は細胞死、PLD系は細胞の機能維持に作用していることが推測される。一方、PC12細胞ではアポトーシスを誘導する活性酸素種のひとつであるH_2O_2によりチロシンキナーゼを介して著しくPLDが活性化されることを明らかにし、Ca^<2+>依存性チロシンキナーゼとして知られているPyk2がPLD活性化に関与するチロシンキナーゼの候補である可能性を見いだし、現在活性化されるPLDアイソザイムの同定も含め、Pyk2との連関を詳細に解析している。また、MAPキナーゼがPLDの活性調節に関与している可能性を示唆する知見を得ており、MAPKKおよびPLDのミュータントを用いてMAPキナーゼとPLDの連関を解析している。一方、脂肪酸型PLD(PLD_<OA>)を主に発現しているヒトT細胞株Jurkat細胞では、アクチノマイシンDなどのアポトーシス刺激により脂肪酸遊離を伴ったPLD活性化を見いだし、PLD_<OA>のアポトーシスにおける役割とその活性化メカニズムを検討している。

Research Products
(20 results)

All Other

All Publications (20 results)

[Publications] Nakashima,S.et al.: "Increased mRNA expression of phospholipase D (PLD) isozymes during granulocytic differentiation of HL60 cells" Biochim.Biophys.Acta. 1389. 173-177 (1998)
[Publications] Yoshimura,S.et al.: "Ceramide formation leads to caspase-3 activation during hypoxic PC12 cell death : Inhibitory effects of Be1-2 on ceramlde formation and caspase-3 activation" J.Biol.Chem.273. 6921-6927 (1998)
[Publications] Sakai,H.et al.: "Molecular cloning of a cDNA encodig a serine protease homologous to complement Cls precursor from rat C6 glial cells and its expression during glial differentiation" Gene. 209. 87-94 (1998)
[Publications] Nakamura,M.et al.: "Involvement of tyrosine phosphorylation in inhibition of fMLP-induced PLD activation by N-acetyl-L-cysteine in differentiated HL-60 cells" J.Leuk.Biol.63. 781-789 (1998)
[Publications] Kanoh,H.et al..: "Molecular cloning of a gene encoding phospholipase D from the pathogenic and dimorphic fungus, Candida albicans" Biochim.Biophys.Acta. 1398. 359-364 (1998)
[Publications] Leidich,S.D.et al.: "Cloning,and disruption of the Candida albicans phospholipase B gene,CaPLB1" J.Biol.Chem.273. 26078-26086 (1998)
[Publications] Wang,S.et al.: "Molecular cloning and cell cycle-dependent expression of a novel NIMA-related protein kinase (TpNrK) in Tetrahymena cells" Biochem.J.334. 197-203 (1998)
[Publications] Mizutani,T.et al.: "Changes in the expression of protein kinase C (PKC) ,phospholipases C (PLC) and D (PLD) isofoms in spleen,Brain and kidney of the aged rat : RT-PCR and Western blot analysis" Mech.Ageing Develop.105. 151-172 (1998)
[Publications] Hayakawa,K.et al.: "Decreased phospholipase D activities in ceramide-induced apoptosis of RBL-2H3 mast cells." Biomed.Res.19. 159-170 (1998)
[Publications] Okamoto,H.et al.: "Studies on blood compatibility of terpolymers composed of methylmethacrylate methoxypolyethyleneglycol methacrylate and dimethylsiloxane methacrylate" J.Biomater.Sci.Polymer Edn.9. 943-959 (1998)
[Publications] Ito,Y.et al.: "Possible involvement of mitogen-activated protein kinase in phospholipase D activation induced by H_2O_2, but not by carbachol, in rat pheochromocytoma PC12 cells" J.Neurochem.71. 2278-2285 (1998)
[Publications] Kasai,T.et al.: "Increased activity of oleate-dependent type phospholipase D during actinomycin D-induced apoptosis in Jurkat T cells" J.Immunol.161. 6469-6474 (1998)
[Publications] Takanaka,K.et al.: "Analysis for phospholipase C gene in patients with subarachnoid hemarrhage due to ruptured intracranial saccular aneurysm" Neurol.Res.(印刷中).
[Publications] Sugiyama,Y.et al.: "Molecular cloning of a second phospholipase B gene,caPLB2 from Candida albicans." J.Med.Mycol.(印刷中).
[Publications] Ohguchi,K.et al.: "Phospholipase D development during differentiation of HL60 cells" Biochim.Biophys.Acta. (印刷中).
[Publications] Nakashima,S.et al.: "Molecular cloning and expression of a stress-responsive MAPK-related kinase from Tetrahymena cells" J.Biol.Chem.(印刷中).
[Publications] Saji,S.et al.: "Overexpression of MDM2 in MCF-7 promotes both growth advantage and p53 accumulation in response to estradiol" Jap.J.Cancer Res.(印刷中).
[Publications] Takenaka,K.et al.: "Polymorphism of the endoglin gene in patients with intracranial saccular sneurysm" J.Neurosurg.(印刷中).
[Publications] Nakashima,S.et al.: "Possible role of phospholipase D(PLD) in cellular differentiation and apoptosis" Chem.Phys.Lipids,. (印刷中).
[Publications] 中島茂他: "ホスホリパーゼDのシグナルトランスダクションのおける役割" 蛋白質核酸酸素. (印刷中).

1998 Fiscal Year Annual Research Report

アポトーシスにおける新規情報変換酵素ホスホリパーゼD(PLD)の役割

Principal Investigator

中島 茂 岐阜大学, 医学部, 助教授 (60188935)

Research Products

[Publications] Nakashima,S.et al.: "Increased mRNA expression of phospholipase D (PLD) isozymes during granulocytic differentiation of HL60 cells" Biochim.Biophys.Acta. 1389. 173-177 (1998)

[Publications] Yoshimura,S.et al.: "Ceramide formation leads to caspase-3 activation during hypoxic PC12 cell death : Inhibitory effects of Be1-2 on ceramlde formation and caspase-3 activation" J.Biol.Chem.273. 6921-6927 (1998)

[Publications] Sakai,H.et al.: "Molecular cloning of a cDNA encodig a serine protease homologous to complement Cls precursor from rat C6 glial cells and its expression during glial differentiation" Gene. 209. 87-94 (1998)

[Publications] Nakamura,M.et al.: "Involvement of tyrosine phosphorylation in inhibition of fMLP-induced PLD activation by N-acetyl-L-cysteine in differentiated HL-60 cells" J.Leuk.Biol.63. 781-789 (1998)

[Publications] Kanoh,H.et al..: "Molecular cloning of a gene encoding phospholipase D from the pathogenic and dimorphic fungus, Candida albicans" Biochim.Biophys.Acta. 1398. 359-364 (1998)

[Publications] Leidich,S.D.et al.: "Cloning,and disruption of the Candida albicans phospholipase B gene,CaPLB1" J.Biol.Chem.273. 26078-26086 (1998)

[Publications] Wang,S.et al.: "Molecular cloning and cell cycle-dependent expression of a novel NIMA-related protein kinase (TpNrK) in Tetrahymena cells" Biochem.J.334. 197-203 (1998)

[Publications] Mizutani,T.et al.: "Changes in the expression of protein kinase C (PKC) ,phospholipases C (PLC) and D (PLD) isofoms in spleen,Brain and kidney of the aged rat : RT-PCR and Western blot analysis" Mech.Ageing Develop.105. 151-172 (1998)

[Publications] Hayakawa,K.et al.: "Decreased phospholipase D activities in ceramide-induced apoptosis of RBL-2H3 mast cells." Biomed.Res.19. 159-170 (1998)

[Publications] Okamoto,H.et al.: "Studies on blood compatibility of terpolymers composed of methylmethacrylate methoxypolyethyleneglycol methacrylate and dimethylsiloxane methacrylate" J.Biomater.Sci.Polymer Edn.9. 943-959 (1998)

[Publications] Ito,Y.et al.: "Possible involvement of mitogen-activated protein kinase in phospholipase D activation induced by H_2O_2, but not by carbachol, in rat pheochromocytoma PC12 cells" J.Neurochem.71. 2278-2285 (1998)

[Publications] Kasai,T.et al.: "Increased activity of oleate-dependent type phospholipase D during actinomycin D-induced apoptosis in Jurkat T cells" J.Immunol.161. 6469-6474 (1998)

[Publications] Takanaka,K.et al.: "Analysis for phospholipase C gene in patients with subarachnoid hemarrhage due to ruptured intracranial saccular aneurysm" Neurol.Res.(印刷中).

[Publications] Sugiyama,Y.et al.: "Molecular cloning of a second phospholipase B gene,caPLB2 from Candida albicans." J.Med.Mycol.(印刷中).

[Publications] Ohguchi,K.et al.: "Phospholipase D development during differentiation of HL60 cells" Biochim.Biophys.Acta. (印刷中).

[Publications] Nakashima,S.et al.: "Molecular cloning and expression of a stress-responsive MAPK-related kinase from Tetrahymena cells" J.Biol.Chem.(印刷中).

[Publications] Saji,S.et al.: "Overexpression of MDM2 in MCF-7 promotes both growth advantage and p53 accumulation in response to estradiol" Jap.J.Cancer Res.(印刷中).

[Publications] Takenaka,K.et al.: "Polymorphism of the endoglin gene in patients with intracranial saccular sneurysm" J.Neurosurg.(印刷中).

[Publications] Nakashima,S.et al.: "Possible role of phospholipase D(PLD) in cellular differentiation and apoptosis" Chem.Phys.Lipids,. (印刷中).

[Publications] 中島 茂他: "ホスホリパーゼDのシグナルトランスダクションのおける役割" 蛋白質核酸酸素. (印刷中).

中島茂岐阜大学, 医学部, 助教授 (60188935)

[Publications] 中島茂他: "ホスホリパーゼDのシグナルトランスダクションのおける役割" 蛋白質核酸酸素. (印刷中).