Role of protein tyrosine kinase in functional changes of hyperplastic arteries

蛋白酪氨酸激酶在增生性动脉功能变化中的作用

基本信息

  • 批准号:
    07660404
  • 负责人:
  • 金额:
    $ 1.41万
  • 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:
    1995
  • 资助国家:
    日本
  • 起止时间:
    1995 至 1996
  • 项目状态:
    已结题

项目摘要

We investigated how protein kinases were involved in functional changes in two kinds of experimentally made hyperplastic arteries. Vascular angioplasty was performed by rubbing the endothelial layr of rabbit carotid artery with a balloon catheter. At 6 weeks of surgery, marked hyperplasia in the intimal layr of the artery was observed. Myosin light chain (MLC) phosphorylation and the contractile response to prostaglandin F2alpha (PGF2alpha) were enhanced in the artery, although the cytosolic Ca^<2+> mobilization was similar to control artery. While serine/threonine kinase inhibitors inhibited the MLC phosphorylation and the contraction in hyperplastic artery than in normal one, tyrosine kinase inhibitors equally inhibited the contraction in both arteries, suggesting that tyrosine kinase was not responsible for the hypercontraction. In a separate experiment, rats were subcutaneously given monocrotaline, which impaired the endothelium of pulmonary artery, resulting in pulmonary hypertens … More ion. Monocrotaline-affected artery showed a marked hyperplasty in the medial layr. In this artery, the relaxing action of the endothelium was markedly impaired. The artery also produced an active tension at the resting state. This active tension was probably due to the membrane depolarization and increased cytosolic Ca^<2+>. The endothelium of the artery seemed to work to increase the resting tension. At some stage, the contractile response to PGF2alpha was enhanced. In this case, tyrosine kinase inhibitors exerted more potent inhibition on the contraction than in the control artery. Thus, tyrosine kinase may be responsible for the abnormal contractility in this type of vascular disease.In addition to the above study we evaluated the selectivity of several protein kinase inhibitors and found that a tyrosine kinase may be involved in PGF2alpha-induced activation of voltage-dependent Ca^<2+> channels in rabbit aorta. We also investigated the mechanism of protein kinase C (PKC)-dependent Ca^<2+> sensitization of contraction. It was suggested that PKC activation and the subsequent release of arachidonic acid inhibit MLC phosphatase, increasing the level of MLC phosphorylation. Tyrosine kinase does not seem to be present in the down-stream of PKC activation. Less
我们研究了蛋白激酶是如何参与两种实验性增生性动脉的功能变化的。血管成形术采用球囊导管摩擦兔颈动脉内皮层的方法。术后6周,动脉内膜明显增生。肌球蛋白轻链(MLC)的磷酸化和对前列腺素F2α(PGF2α)的收缩反应在动脉中得到增强,尽管胞浆Ca~(2+)动员与对照动脉相似。当丝氨酸/苏氨酸激酶抑制剂抑制MLC的磷酸化和收缩时,酪氨酸激酶抑制剂同样抑制两条动脉的收缩,提示酪氨酸激酶不是导致血管过度收缩的原因。在另一项实验中,大鼠皮下注射野百合碱,它损害了肺动脉内皮细胞,导致肺高压…。更多的离子。野百合碱影响的动脉内侧层有明显的肥大。在这条动脉中,内皮的松弛作用明显受损。在静息状态下,动脉也产生主动张力。这种主动张力可能是由于膜去极化和胞内Ca~(2+)&Gt;升高所致。动脉内皮细胞似乎起到增加静息张力的作用。在某些阶段,对PGF2α的收缩反应增强。在这种情况下,酪氨酸激酶抑制剂对收缩的抑制作用比对照动脉更强。因此,酪氨酸激酶可能与这类血管疾病的异常收缩有关。除了上述研究,我们还评估了几种蛋白激酶抑制剂的选择性,发现酪氨酸激酶可能参与了PGF2pha诱导的兔主动脉电压依赖性钙通道的激活。我们还研究了蛋白激酶C(PKC)依赖的钙敏感性收缩的机制。提示PKC的激活和随后花生四烯酸的释放抑制了MLC磷酸酶,增加了MLC的磷酸化水平。酪氨酸激酶似乎不存在于PKC激活的下游。较少

项目成果

期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Asano,M.,Matsunaga,K.,Ito,K.et al.: "Selectivity of action staurosporine on Ca^<2+> movements and contractions in vascular smooth muscles" Eur.J.Pharmacol.294(2/3). 693-701 (1995)
Asano,M.,Matsunaga,K.,Ito,K.等人:“星形孢菌素对血管平滑肌 Ca^2 运动和收缩的选择性”Eur.J.Pharmacol.294(2/3)。
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    0
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Asano,M.,Ito,K.et al.: "Selectivity of action of staurosporine on Ca^<2+> movements and contractions in vascular smooth muscles" Eur.J.Pharmacol.294. 693-701 (1995)
Asano,M.,Ito,K.等人:“星形孢菌素对血管平滑肌中 Ca^2 运动和收缩的选择性作用”Eur.J.Pharmacol.294。
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    0
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Asano, M.et al.: "Selectivity of action of staurosporine on Ca^<2+> movements and contractions in vascular smooth muscles" Eur.J.Pharmacol. 294(2/3). 693-701 (1995)
Asano, M.等人:“星形孢菌素对血管平滑肌中 Ca^2 运动和收缩的选择性作用”Eur.J.Pharmacol。
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    0
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Seto, M.et al.: "Selective inhibition of myosin phosphorylation and tension of hyperplastic arteries by the kinase inhibitor HA1077" Eur.J.Pharmacol. 276(1). 27-33 (1995)
Seto, M.et al.:“激酶抑制剂 HA1077 对肌球蛋白磷酸化和增生动脉张力的选择性抑制”Eur.J.Pharmacol。
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Seto,K.,Shindo,K.,Ito,K.,et al.: "Selective inhibition of myosin phosphorylation and tension of hyperplastic arteries by the kinase inhibitor HA1077" Eur.J.Pharmacol.276(1). 27-33 (1995)
Seto,K.、Shindo,K.、Ito,K. 等人:“激酶抑制剂 HA1077 对肌球蛋白磷酸化和增生动脉张力的选择性抑制”Eur.J.Pharmacol.276(1)。
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ITO Katsuaki其他文献

ITO Katsuaki的其他文献

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{{ truncateString('ITO Katsuaki', 18)}}的其他基金

The role of P2X receptor in overactive bladder and application of drugs targeting the receptor
P2X受体在膀胱过度活动症中的作用及靶向药物的应用
  • 批准号:
    21580365
  • 财政年份:
    2009
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Significance of cross-talk among ADP, thromboxane A2 and collagen during collagen-induced thrombus formation
胶原诱导血栓形成过程中 ADP、血栓素 A2 和胶原之间串扰的意义
  • 批准号:
    17580258
  • 财政年份:
    2005
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Studies on the signal transduction system of platelet collagen receptor that is related to species difference of hemostasis
与止血种属差异相关的血小板胶原受体信号转导系统的研究
  • 批准号:
    15580261
  • 财政年份:
    2003
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Characteristics of aggregation of bovine platelets and clarification of molecular mechanism responsible for a genetic hemorrhagic disease in cattle
牛血小板聚集特征及牛遗传性出血病分子机制的阐明
  • 批准号:
    12660272
  • 财政年份:
    2000
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Biological significance of palytoxin-sensitive ion channel associated with NaィイD1+ィエD1,KィイD1+ィエD1-ATPase molecule
NaiiD1+IeD1、KiiD1+IeD1-ATPase分子相关的海藻毒素敏感离子通道的生物学意义
  • 批准号:
    09460140
  • 财政年份:
    1997
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
The role of plasmalemmal Ca^<2+> channels and intracellular Ca^<2+> stores in vascular smooth muscles during the development of vascular resistance
血管平滑肌质膜Ca^2通道和细胞内Ca^2储存在血管阻力发展过程中的作用
  • 批准号:
    04660325
  • 财政年份:
    1992
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Cellular calcium movements and the role in regulating contraction and relaxation of vascular smooth muscles of resistance vessels
细胞钙运动及其调节阻力血管平滑肌收缩和舒张的作用
  • 批准号:
    02660312
  • 财政年份:
    1990
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Studies on the alterations of lung endothelial cells and the metabolism of autacoids during lung diseases
肺部疾病过程中肺内皮细胞变化及自体物质代谢的研究
  • 批准号:
    60480095
  • 财政年份:
    1985
  • 资助金额:
    $ 1.41万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)

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Temperature alteration in the anterior chamber and corneal endothelium injury during phacoemulsification
超声乳化手术过程中前房温度变化和角膜内皮损伤
  • 批准号:
    15K10851
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Interaction between the endothelium injury of pulmonary vessels and the activated platelets on the formation of post operative pulmonary embolism
肺血管内皮损伤与活化血小板的相互作用对术后肺栓塞形成的影响
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Identification and characterization of Shinga toxin-independent virulence factors of enterohemorrhagic Escherichia coli which contribute to vascular endothelium injury
导致血管内皮损伤的肠出血性大肠杆菌辛加毒素非依赖性毒力因子的鉴定和表征
  • 批准号:
    5390014
  • 财政年份:
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