1999 年度実績報告書

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

研究課題

研究課題/領域番号	10670136
研究機関	岐阜大学
研究代表者	中島茂岐阜大学, 医学部, 教授 (60188935)
研究分担者	坂野喜子岐阜大学, 医学部, 助教授 (50116852)
キーワード	ホスホリパーゼD / アポトーシス / 細胞分化 / セラミド / 酸化ストレス
研究概要	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。また、従来遺伝子の障害によると考えられていた放射線障害による細胞死にも、SMアーゼが中心的な役割を果たしている可能性が示された。一方、アルツハイマー病患者脳や老化した線維芽細胞では著しいホスホリパーゼD(PLD)活性の低下が示されており、細胞の機能維持・生存にPLDの重要性が示唆されている。ラットグリオーマ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、ラット好塩基球性白血病RBL-2H3細胞、ラット褐色細胞腫PC12細胞、ヒト表皮HaCat細胞など他の細胞系、あるいは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。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、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。一方、脂肪酸型PLDを主に発現しているJurkat T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、脂肪酸型PLD(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。以上の結果から、セラミド系のみならず、PLD系も細胞の生存・アポトーシスの重要な調節因子として機能していることが推測される。

研究成果

(32件)

すべてその他

すべて文献書誌 (32件)

[文献書誌] 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)
[文献書誌] Yoshimura, S.Et al.: "Ceramide formation leads to caspase-3 activation during hypoxic PC12 cell death:Inhibitory effects of Bcl-2 on ceramide formation and caspase-3 activation"J.Biol.Chem.. 273. 6921-6927 (1998)
[文献書誌] Sakai, H.Et al.: "Molecular cloning of a cDNA encodig a serine protease homologous to complement C1s precursor from rat C6 glial cells and its expression during glial differentiation"Gene. 209. 87-94 (1998)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Leidich, S.D.Et al.: "Cloning,and disruption of the Candida albicans phospholipase B gene,CaPLB1"J.Biol.Chem.. 273. 26078-26086 (1998)
[文献書誌] 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)
[文献書誌] Mizutani, T.Et al.: "Changes in the expression of protein kinase C(PKC),phospholipases C(PLC)andD(PLD)isofoms in spleen,brain and kidney of the aged rat"Mech.Ageing Develop.. 105. 151-172 (1998)
[文献書誌] Hayakawa, K.Et al.: "Decreased phospholipase D activities in ceramide-induced apoptosis of RBL-2H3 mast cells."Biomed.Res.. 19. 159-170 (1998)
[文献書誌] Okamoto, H. Et al.: "Studies on blood compatibility of terpolymers compased of methylmethacrylate methoxypolyethyleneglycol methacrylate and dimethylsiloxane methacrylate"J.Biomater.Sci.Polymer Edn.. 9. 943-959 (1998)
[文献書誌] 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 PC12 cells"J.Neurochem.. 71. 2278-2285 (1998)
[文献書誌] 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)
[文献書誌] Takanaka, K. Et al.: "Analysis for phospholipase C gene in patients with subarachnoid hemarrhage due to ruptured intracranial saccular aneurysm"Neurol.Res.. 21. 368-372 (1999)
[文献書誌] Sugiyama, Y.Et al.: "Molecular cloning of a second phospholipase B gene,caPLB2 from Cacdida albicans."Med.Mycol.. 37. 61-67 (1999)
[文献書誌] Ohguchi, K.Et al.: "Phospholipase D development during differentiation of HL60 cells"Biochim.Biophys.Acta. 1439. 215-228 (1999)
[文献書誌] Nakashima, S.Et al.: "Molecular cloning and expression of a stress-responsive MAPK-related kinase from Tetrahymena cells"J.Biol.Chem.. 274. 9976-9983 (1999)
[文献書誌] 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.. 90. 210-218 (1999)
[文献書誌] Takenaka, K.Et al.: "Polymorphism of the endoglin gene in patients with intracranial saccular sneurysm"J.Neurosurg.. 90. 935-938 (1999)
[文献書誌] Nakashima, S.Et al.: "Possible role of phospholipase D(PLD)in cellular differentiation and apoptosis"Chem.Phys.Lipids. 98. 153-164 (1999)
[文献書誌] Hayakawa, K.Et al.: "Increased expression of phospholipase D1 mRNA during cAMP-or NGF-induced differentiation in PC12 cells."Neurosci.Lett.. 265. 127-130 (1999)
[文献書誌] Yoshimura, S.Et al.: "Inhibition of neutral sphingomyelinase activation and ceramide formation by glutathione in hypoxic neuronal cell death"J.Neurochem.. 73. 675-683 (1999)
[文献書誌] Kumada, H. Et al.: "Hydorgen peroxide-induced phospholipase D activation in human vascular smooth muscle cells"Biomed.Res.. 20. 87-98 (1999)
[文献書誌] Wang S.Et al.: "Molecular cloning and cell-cycle-dependent expression of the acetyl-CoA synthetase gene in Tetrahymena cells"Biochem.J.. 343. 479-485 (1999)
[文献書誌] Zhao, Y. Et al.: "Molecular cloning of a cDNA encoding 14-3-3 protein from the protozoan Tetrahymena pyriformis and its mRNA expression during synchronous division"Gene. 234. 209-215 (1999)
[文献書誌] Banno, Y. Et al.: "Differential phospholipase D activation by bradykinin and sphingosine 1-phosphate in NIH 3T3 fibroblasts overexpressing gelsolin"J.Biol.Chem.. 274. 27385-27391 (1999)
[文献書誌] Tan, Z. Et al.: "The effects of local anesthetics on phospholipase D activity in differentiated human promyelocytic leukemic HL60 cells"Biochem.Pharmacol.. 58. 1881-1889 (1999)
[文献書誌] Tan, Z. Et al.: "Local anethetics inhibit muscarinic receptor-mediated activation of extracellular signal-regulated kinases(ERKs)in rat pheochromocytoma PC12 cells"Anethesiology. 91. 1014-1024 (1999)
[文献書誌] Wang, S. Et al.: "Stress-responsive changes in the mRNA levels of MAPK-related protein kinase(TpMAPK)and NIMA-related protein kinase(TpNrk)in Tetrahymena cells"Europ.J.Protistol.. 35. 275-280 (1999)
[文献書誌] Nakamura, Y.Et al.: "Stimulatory effect of cytochalasin D on antigen-induced phospholipase D activation in a murine mast cell model(RBL-2H3)"Allergology International. 48. 139-245 (1999)
[文献書誌] Nagaki, M. Et al.: "Lethal hepatic apoptosis mediated by tumor necrosis factor receptor,unlike Fas-mediated apoptosis,requires hepatocyte sensitization in mice"J,Hepatol.. 31. 997-1005 (1999)
[文献書誌] Yamakawa, H. Et al.: "Activation of caspase-9 and -3 during H_2O_2-induced apoptosis of PC12 cells independnent of ceramide formation"Neurol.Res.. 印刷中.
[文献書誌] 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における役割"蛋白質核酸酵素. 44. 998-1006 (1999)

1999 年度 実績報告書

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

研究代表者

中島 茂 岐阜大学, 医学部, 教授 (60188935)

研究成果

[文献書誌] 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)

[文献書誌] Yoshimura, S.Et al.: "Ceramide formation leads to caspase-3 activation during hypoxic PC12 cell death:Inhibitory effects of Bcl-2 on ceramide formation and caspase-3 activation"J.Biol.Chem.. 273. 6921-6927 (1998)

[文献書誌] Sakai, H.Et al.: "Molecular cloning of a cDNA encodig a serine protease homologous to complement C1s precursor from rat C6 glial cells and its expression during glial differentiation"Gene. 209. 87-94 (1998)

[文献書誌] 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)

[文献書誌] 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)

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

[文献書誌] 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)

[文献書誌] Mizutani, T.Et al.: "Changes in the expression of protein kinase C(PKC),phospholipases C(PLC)andD(PLD)isofoms in spleen,brain and kidney of the aged rat"Mech.Ageing Develop.. 105. 151-172 (1998)

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

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

[文献書誌] 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 PC12 cells"J.Neurochem.. 71. 2278-2285 (1998)

[文献書誌] 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)

[文献書誌] Takanaka, K. Et al.: "Analysis for phospholipase C gene in patients with subarachnoid hemarrhage due to ruptured intracranial saccular aneurysm"Neurol.Res.. 21. 368-372 (1999)

[文献書誌] Sugiyama, Y.Et al.: "Molecular cloning of a second phospholipase B gene,caPLB2 from Cacdida albicans."Med.Mycol.. 37. 61-67 (1999)

[文献書誌] Ohguchi, K.Et al.: "Phospholipase D development during differentiation of HL60 cells"Biochim.Biophys.Acta. 1439. 215-228 (1999)

[文献書誌] Nakashima, S.Et al.: "Molecular cloning and expression of a stress-responsive MAPK-related kinase from Tetrahymena cells"J.Biol.Chem.. 274. 9976-9983 (1999)

[文献書誌] 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.. 90. 210-218 (1999)

[文献書誌] Takenaka, K.Et al.: "Polymorphism of the endoglin gene in patients with intracranial saccular sneurysm"J.Neurosurg.. 90. 935-938 (1999)

[文献書誌] Nakashima, S.Et al.: "Possible role of phospholipase D(PLD)in cellular differentiation and apoptosis"Chem.Phys.Lipids. 98. 153-164 (1999)

[文献書誌] Hayakawa, K.Et al.: "Increased expression of phospholipase D1 mRNA during cAMP-or NGF-induced differentiation in PC12 cells."Neurosci.Lett.. 265. 127-130 (1999)

[文献書誌] Yoshimura, S.Et al.: "Inhibition of neutral sphingomyelinase activation and ceramide formation by glutathione in hypoxic neuronal cell death"J.Neurochem.. 73. 675-683 (1999)

[文献書誌] Kumada, H. Et al.: "Hydorgen peroxide-induced phospholipase D activation in human vascular smooth muscle cells"Biomed.Res.. 20. 87-98 (1999)

[文献書誌] Wang S.Et al.: "Molecular cloning and cell-cycle-dependent expression of the acetyl-CoA synthetase gene in Tetrahymena cells"Biochem.J.. 343. 479-485 (1999)

[文献書誌] Zhao, Y. Et al.: "Molecular cloning of a cDNA encoding 14-3-3 protein from the protozoan Tetrahymena pyriformis and its mRNA expression during synchronous division"Gene. 234. 209-215 (1999)

[文献書誌] Banno, Y. Et al.: "Differential phospholipase D activation by bradykinin and sphingosine 1-phosphate in NIH 3T3 fibroblasts overexpressing gelsolin"J.Biol.Chem.. 274. 27385-27391 (1999)

[文献書誌] Tan, Z. Et al.: "The effects of local anesthetics on phospholipase D activity in differentiated human promyelocytic leukemic HL60 cells"Biochem.Pharmacol.. 58. 1881-1889 (1999)

[文献書誌] Tan, Z. Et al.: "Local anethetics inhibit muscarinic receptor-mediated activation of extracellular signal-regulated kinases(ERKs)in rat pheochromocytoma PC12 cells"Anethesiology. 91. 1014-1024 (1999)

[文献書誌] Wang, S. Et al.: "Stress-responsive changes in the mRNA levels of MAPK-related protein kinase(TpMAPK)and NIMA-related protein kinase(TpNrk)in Tetrahymena cells"Europ.J.Protistol.. 35. 275-280 (1999)

[文献書誌] Nakamura, Y.Et al.: "Stimulatory effect of cytochalasin D on antigen-induced phospholipase D activation in a murine mast cell model(RBL-2H3)"Allergology International. 48. 139-245 (1999)

[文献書誌] Nagaki, M. Et al.: "Lethal hepatic apoptosis mediated by tumor necrosis factor receptor,unlike Fas-mediated apoptosis,requires hepatocyte sensitization in mice"J,Hepatol.. 31. 997-1005 (1999)

[文献書誌] Yamakawa, H. Et al.: "Activation of caspase-9 and -3 during H_2O_2-induced apoptosis of PC12 cells independnent of ceramide formation"Neurol.Res.. 印刷中.

[文献書誌] 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における役割"蛋白質核酸酵素. 44. 998-1006 (1999)

1999 年度実績報告書

中島茂岐阜大学, 医学部, 教授 (60188935)

[文献書誌] 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における役割"蛋白質核酸酵素. 44. 998-1006 (1999)