Mitogen-activated protein kinase mediation of hemolysate-induced contraction in rabbit basilar artery.
Mitogen-activated protein kinase mediation of hemolysate-induced contraction in rabbit basilar artery.
复制标题
丝裂原激活蛋白激酶介导溶血诱导的兔基底动脉收缩。
DOI：
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复制
发表时间：
1999
影响因子：
4.1
通讯作者：
John H. Zhang
中科院分区：
文献类型：
--
作者：
A. Zubkov;K. Ogihara;P. Tumu;Anita Patlolla;Adam I Lewis;A. Parent;John H. Zhang
对象
丝裂原活化蛋白激酶（MAPK）是血管增殖和收缩的重要信号传导因子，而血管增殖和收缩是蛛网膜下腔出血后脑血管痉挛的两个特征。作者研究了丝裂原活化蛋白激酶（MAPK）在溶血物引起的兔基底动脉（BA）收缩信号转导中的作用。
方法
用等长张力记录兔BA对溶血产物的收缩反应，并使用MAPK抗体获得Western印迹。报告了以下结果。1)溶血产生浓度依赖性收缩兔BA，然而，预孵育的动脉与MAPK激酶（MEK）抑制剂PD-98059显着减少这种收缩。PD-98059给药还以浓度依赖性方式缓解了10%溶血产物诱导的持续收缩。2)Janus酪氨酸激酶2抑制剂AG-490与动脉环预孵育，减少了对溶血产物的收缩反应，但未能放松该药剂诱导的持续收缩。Src-酪氨酸激酶抑制剂damnacanthal和磷脂酰肌醇3-激酶抑制剂wortmannin未能减少溶血引起的收缩。3)溶血产物产生的MAPK免疫反应性的时间依赖性升高，如兔BA的Western印迹所示。在溶血产物暴露后1分钟，MAPK增强，并且在5分钟时达到最大水平。MAPK的免疫反应性随着时间的推移衰减缓慢，但这种激酶的水平仍然高于基础水平，即使在暴露于溶血产物后2小时。用MEK抑制剂PD-98059预孵育动脉可消除溶血产物对MAPK免疫反应性的影响。
结论
溶血产物引起的兔BA收缩，可能是通过激活MAPK，因此MAPK抑制剂可用于治疗脑血管痉挛。
OBJECT
Mitogen-activated protein kinase (MAPK) is an important signaling factor in vascular proliferation and contraction, which are the two features of cerebral vasospasm that follow subarachnoid hemorrhage. The authors studied the possible involvement of MAPK in hemolysate-induced signal transduction and contraction in rabbit basilar artery (BA).
METHODS
Isometric tension was used to record the contractile response of rabbit BA to hemolysate, and Western blots were obtained using antibodies for MAPK. The following results are reported. 1) Hemolysate produced a concentration-dependent contraction of rabbit BA; however, preincubation of arteries with the MAPK kinase (MEK) inhibitor PD-98059 markedly reduced this contraction. The administration of PD-98059 also relaxed, in a concentration-dependent fashion, the sustained contraction induced by 10% hemolysate. 2) The Janus tyrosine kinase 2 inhibitor AG-490, preincubated with arterial rings, reduced the contractile response to hemolysate but failed to relax the sustained contraction induced by this agent. The Src-tyrosine kinase inhibitor damnacanthal and the phosphatidylinositol 3-kinase inhibitor wortmannin failed to reduce hemolysate-induced contraction. 3) Hemolysate produced a time-dependent elevation of MAPK immunoreactivity as seen on Western blots of rabbit BA. The MAPK was enhanced 1 minute after hemolysate exposure and the effect reached maximum levels at 5 minutes. The immunoreactivity of MAPK decayed slowly over time, but the level of this kinase was still higher than the basal level, even at 2 hours after exposure to hemolysate. Preincubation of arteries with the MEK inhibitor PD-98059 abolished the effect of hemolysate on MAPK immunoreactivity.
CONCLUSIONS
Hemolysate produced contraction of rabbit BA, possibly by activation of MAPK, and therefore MAPK inhibitors may be useful in the treatment of cerebral vasospasm.
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DOI：
10.1152/ajpheart.1995.269.6.h1874
发表时间：
1995-12
期刊：
The American journal of physiology
影响因子：
--
作者：
H. Zhang;B. Weir;L. Marton;R. Macdonald;V. Bindokas;R. Miller;J. Brorson
通讯作者：
H. Zhang;B. Weir;L. Marton;R. Macdonald;V. Bindokas;R. Miller;J. Brorson
影响因子：
8.3
作者：
Force, T;Bonventre, JV
通讯作者：
Bonventre, JV
动脉平滑肌收缩刺激激活蛋白激酶 C 同工酶。
影响因子：
3.9
作者：
Singer,HA;Schworer,CM;Sweeley,C;Benscoter,H
通讯作者：
Benscoter,H
影响因子：
8.3
作者：
Griendling, KK;UshioFukai, M;Alexander, RW
通讯作者：
Alexander, RW
影响因子：
20.1
作者：
M. Ishida;Takafumi Ishida;Sheila M. Thomas;Bradford C. Berk
通讯作者：
M. Ishida;Takafumi Ishida;Sheila M. Thomas;Bradford C. Berk