Studies on the mechanism for regulation of phospholipase A_2 activation by ceramide
神经酰胺调控磷脂酶A_2活化的机制研究
基本信息
- 批准号:12672135
- 负责人:
- 金额:$ 2.11万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2000
- 资助国家:日本
- 起止时间:2000 至 2002
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
In the study, the regulatory mechanism of cytosolic phospholipase A_2 (cPLA_2) by ceramide, and the implication of ceramide in the pathogenesis of atherosclerosis and nephropathy via acceleration of cPLA_2 activation were investigated. The results obtained are as follows.1) When rabbit platelets were stimulated with Ca^<2+> ionophore or Ca^<2+> was added into platelet lysate, Ca^<2+>-dependent association of cPLA_2 with platelet membranes was assessed by increase in cPLA_2 protein using immunoblot analysis and in the activity in membranes. Ceramide apparently increased the association.2) In rat basophilic leukemia cells stimulated with antigen, ceramide accelerated orthovanadate-sensitive protein tyrosine phosphatase activation, which induces dephosphorylation of extracellular signal-regulated kinase 1/2 to attenuate the potency of cPLA_2 activation. Furthermore, ceramide suppressed antigen-induced phospholipase D activation and subsequent formation of phosphatidic acid, which is chara … More cterized to be substrate for cPLA_2. These events lead to decrease in cPLA_2 activity, hence, providing evidence that ceramide acts as a negative regulator in agonist-stimulated cPLA_2 activation.3) Cholesterol ester formation stimulated by the uptake of oxidized low-density lipoproteins in macrophages was fully dependent on cPLA_2 activation. Under the condition de novo synthesis of ceramide was elicited. Furthermore, pretreatment of the cells with sphingomyelinase enhanced the ester formation. These results indicate that de novo-synthesized ceramide accelerates cholesterol ester formation via cPLA_2 activation leading to foam cell formation, and suggest that ceramide is implicated in the initiation and development of atherosclerosis.4) Stimulation of mesangial cells with tumor necrosis factor α (TNFα) increased expression of cyclooxygenase-2 and secretory PLA_2 following activation of transcription factor, nuclear factor-κB. Pretreatment of the cells with sphingomyelinase enhanced these responses and the enhancement was fully dependent on the production of reactive oxygen species. TNFα also activated sphingomyelinase to produce ceramide from sphingomyelin. These results suggest that ceramide facilitates production of prostaglandins and is implicated in the pathogenesis of renal diseases. Less
本研究旨在探讨神经酰胺对胞浆型磷脂酶A_2(cPLA_2)的调节机制,以及神经酰胺通过促进cPLA_2活化在动脉粥样硬化和肾病发病中的作用。结果如下:(1)用Ca^<2+>离子载体刺激兔血小板,或在血小板溶解液中加入Ca^<2+>,通过免疫印迹分析测定血小板膜上cPLA_2蛋白的增加和膜上cPLA_2活性的增加,来评价血小板膜与cPLA_2的Ca^<2+>依赖性结合。2)在抗原刺激的大鼠嗜碱性白血病细胞中,神经酰胺促进原钒酸敏感蛋白酪氨酸磷酸酶的激活,使细胞外信号调节激酶1/2去磷酸化,从而减弱cPLA_2的激活能力。此外,神经酰胺抑制抗原诱导的磷脂酶D激活和随后的磷脂酸形成,这是一种特异性的抑制剂。 ...更多信息 鉴定为cPLA_2的底物。3)巨噬细胞摄取氧化型低密度脂蛋白刺激的胆固醇酯生成完全依赖于cPLA_2的激活。在此条件下,神经酰胺的从头合成被引发。此外,用鞘磷脂酶预处理细胞增强了酯的形成。提示神经酰胺通过激活cPLA_2促进胆固醇酯的形成,从而导致泡沫细胞的形成,提示神经酰胺参与了动脉粥样硬化的发生和发展。4)用肿瘤坏死因子α(TNFα)刺激系膜细胞,可激活核因子-κB,增加环氧化酶-2的表达和分泌PLA_2。用鞘磷脂酶预处理细胞增强了这些反应,并且这种增强完全依赖于活性氧的产生。TNFα还激活鞘磷脂酶,从鞘磷脂产生神经酰胺。这些结果表明,神经酰胺促进了三尖杉酯碱的产生,并与肾脏疾病的发病机制有关。少
项目成果
期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kazuyuki KITATANI: "Acceleration by ceramide of calcium-dependent translocation of phospholipase A_2 from cytosol to membranes in platelets."Arch.Biochem.Biophys.. 382・2. 296-302 (2000)
Kazuyuki KITATANI:“通过神经酰胺加速磷脂酶 A_2 从细胞质到血小板膜的易位。”Arch.Biochem.Biophys.. 382・2 (2000)。
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Kazuyuki Kitatani: "Ceramide accelerates dephosphorylation of extracellular signal-regulated kinase 1/2 to decrease prostaglandin D_2 production in RBL-2H3 cells"Arch.Biochem.Biophys.. 395. 208-214 (2001)
Kazuyuki Kitatani:“神经酰胺加速细胞外信号调节激酶 1/2 的去磷酸化,以减少 RBL-2H3 细胞中前列腺素 D_2 的产生”Arch.Biochem.Biophys.. 395. 208-214 (2001)
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Kazuyuki Kitatani: "Ceramide accelerates dephosphorylation of extracellular signal-regulated kinase 1/2 to decrease prostaglandin D2 production in RBL-2H3 cells"Arch. Biochem. Biophys.. 395-2. 208-214 (2001)
Kazuyuki Kitatani:“神经酰胺加速细胞外信号调节激酶 1/2 的去磷酸化,以减少 RBL-2H3 细胞中前列腺素 D2 的产生”Arch。
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Kazuyuki Kitatani: "Stimulation by de novo-synthesized ceramide of phospholipase A_2-dependent cholesterol esterification promoted by the uptake of oxidized low-density lipoprotein in macrophages"Cell.Signal.. 14. 695-701 (2002)
Kazuyuki Kitatani:“巨噬细胞中氧化低密度脂蛋白的摄取促进磷脂酶 A_2 依赖性胆固醇酯化的从头合成神经酰胺的刺激”Cell.Signal.. 14. 695-701 (2002)
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Kazuyuki Kitatani: "Role of phospholipase D-derived phosphatidic acid as a substrate for phospholipase A_2 in RBL-2H3 cells"Biol. Pharm. Bull.. 23-12. 1430-1433 (2001)
Kazuyuki Kitatani:“磷脂酶 D 衍生的磷脂酸作为 RBL-2H3 细胞中磷脂酶 A_2 底物的作用”Biol。
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SATO Takashi其他文献
Proposal and Trial of Vocational Training for Industrial Robot Technician Compatible with the Smart Factory
与智能工厂相适应的工业机器人技术人员职业培训的建议与尝试
- DOI:
10.4307/jsee.68.1_75 - 发表时间:
2020 - 期刊:
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SATO Takashi;KIKUCHI Takuo;TAKAHASHI Koji - 通讯作者:
TAKAHASHI Koji
ものづくりアスリートのためのスキルテックを活用した訓練法の動向調査
使用技能技术培养运动员的训练方法趋势调查
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2023 - 期刊:
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SATO Takashi;KIKUCHI Takuo;TAKAHASHI Koji;島田貴仁・高木大資・讃井知・春田悠佳;菊池拓男 - 通讯作者:
菊池拓男
Covid-19 による高齢者の対人相互作用および日常活動の変化 パンデミック前後のパネル調査による個人要因・地区要因の検討
Covid-19导致老年人人际交往和日常活动的变化通过疫情前后的小组调查考察个人和地区因素
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2022 - 期刊:
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SATO Takashi;KIKUCHI Takuo;TAKAHASHI Koji;島田貴仁・高木大資・讃井知・春田悠佳 - 通讯作者:
島田貴仁・高木大資・讃井知・春田悠佳
Lung epithelial fucosylation promotes the development of house dust mite (HDM)-induced allergic airway inflammation
肺上皮岩藻糖基化促进屋尘螨(HDM)诱导的过敏性气道炎症的发展
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- 发表时间:
2017 - 期刊:
- 影响因子:0
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SAKU Aiko;HIROSE Koichi;ITO Takashi;SATO Takashi;GOTO Yoshiyuki;KIYONO Hiroshi;NAKAJIMA Hiroshi - 通讯作者:
NAKAJIMA Hiroshi
SATO Takashi的其他文献
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{{ truncateString('SATO Takashi', 18)}}的其他基金
Peptide ligand screening of transthyretin protein-protein interaction inhibitor using phage display system
利用噬菌体展示系统筛选转甲状腺素蛋白-蛋白质相互作用抑制剂的肽配体
- 批准号:
16K18875 - 财政年份:2016
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$ 2.11万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Study of nanoparticles-incorporating immune modulating oligodeoxynucleotide for the treatment of lung diseases
纳米颗粒掺入免疫调节寡脱氧核苷酸治疗肺部疾病的研究
- 批准号:
15K09224 - 财政年份:2015
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$ 2.11万 - 项目类别:
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Evolution of the new competition policy by the open source strategy
开源战略演变新竞争政策
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25380313 - 财政年份:2013
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Development of drugs targeting secretory inhibition of transthyretin for familial amyloidotic polyneuropathy
开发针对家族性淀粉样变性多发性神经病的运甲状腺素蛋白分泌抑制药物
- 批准号:
24790079 - 财政年份:2012
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$ 2.11万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Study of inhaled nanoparticles incorporating synthetic oligodeoxynucleotides to treat lung diseases
掺入合成寡脱氧核苷酸的吸入纳米颗粒治疗肺部疾病的研究
- 批准号:
23790917 - 财政年份:2011
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$ 2.11万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
A Study in Dynamics of BEI Expression in 3 Prefectures in Northern Kanto Region
北关东地区3县BEI表达动态研究
- 批准号:
23520564 - 财政年份:2011
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$ 2.11万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Investigation for the nuculear receptor functions to cure clonic inflammatory syndrome
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- 批准号:
23591347 - 财政年份:2011
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$ 2.11万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Stabilization and Emergence of Rule Dynamics in Dynamic Cognitive Agents with Internal Dynamics
具有内部动力学的动态认知主体中规则动力学的稳定和出现
- 批准号:
22700242 - 财政年份:2010
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$ 2.11万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Oscillation characteristics improvement of a Vertical Cavity Surface Emitting Laser and consideration to its application
垂直腔面发射激光器振荡特性的改进及其应用思考
- 批准号:
22560035 - 财政年份:2010
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$ 2.11万 - 项目类别:
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Molecular mechanisms of gefitinib-induced rash formation: Gefitinib augments lipogenesis and steroidgenesis in sebaceous glands
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22590506 - 财政年份:2010
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$ 2.11万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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