Trypanosoma cruzi infection (Chagas' disease) of mice causes activation of the mitogen-activated protein kinase cascade and expression of endothelin-1 in the myocardium.
Trypanosoma cruzi infection (Chagas' disease) of mice causes activation of the mitogen-activated protein kinase cascade and expression of endothelin-1 in the myocardium.
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小鼠的克氏锥虫感染（恰加斯病）会导致心肌细胞中有丝分裂原激活蛋白激酶级联的激活和内皮素-1 的表达。
DOI：
10.1097/00005344-200036051-00046
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发表时间：
2000
影响因子：
3
通讯作者：
Tanowitz,HB
中科院分区：
文献类型：
--
作者：
Huang,H;Petkova,SB;Pestell,RG;Bouzahzah,B;Chan,J;Magazine,H;Weiss,LM;Christ,GJ;Lisanti,MP;Douglas,SA;Shtutin,V;Halonen,SK;Wittner,M;Tanowitz,HB
查加斯病由寄生虫克氏锥虫引起，是心脏病的重要原因。该实验室先前的研究表明，在感染小鼠中观察到微血管痉挛和心肌缺血。用这种寄生虫感染内皮细胞增加了生物活性内皮素-1（ET-1）的合成。因此，在T.在Cruzi感染的小鼠中，我们检测了ET-1的表达和调节ET-1表达的p42/44-丝裂原活化蛋白激酶（MAPK）-AP-1通路。感染C57 BL/6小鼠心肌有寄生虫和心肌坏死。逆转录聚合酶链反应（RT-PCR）分析显示转录因子AP-1（c-jun和c-fos）的mRNA表达升高，电泳迁移率变动分析（EMSA）测定AP-1 DNA结合活性增加。蛋白质印迹分析表明，细胞外信号调节激酶（ERK 1/2）的磷酸化形式的增加。感染小鼠心肌ET-1 mRNA表达上调。免疫组织化学和免疫电镜检测到ET-1在心肌细胞和内皮细胞中的表达增加。这些结果提示ET-1参与了心肌病的发生，ET-1表达增加的机制是T.克氏感染
Chagas' disease, caused by the parasite Trypanosoma cruzi, is an important cause of heart disease. Previous studies from this laboratory revealed that microvascular spasm and myocardial ischemia were observed in infected mice. Infection of endothelial cells with this parasite increased the synthesis of biologically active endothelin-1 (ET-1). Therefore, in the myocardium of T. cruzi-infected mice, we examined ET-1 expression and the p42/44-mitogen activated protein kinase (MAPK)-AP-1 pathway that regulates the expression of ET-1. There was parasitism and myonecrosis in the myocardium of infected C57BL/6 mice. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed elevated mRNA expression of transcription factor AP-1 (c-jun and c-fos) and increased AP-1 DNA binding activity as determined by electrophoretic mobility shift assay (EMSA). Western blot analysis demonstrated an increase in the phosphorylated forms of extracellular signal-regulated kinase (ERK1/2). ET-1 mRNA was upregulated in the myocardium of infected mice. Immunohistochemical and immunoelectron microscopy using anti-ET-1 antibody detected increased expression in cardiac myocytes and endothelium of these mice. These data suggest that ET-1 contributes to chagasic cardiomyopathy and that the mechanism of the increased expression of ET-1 is a result of the activation of the MAPK pathway by T. cruzi infection.