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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Ethyl isopropyl amiloride inhibits smooth muscle cell proliferation and migration by inducing apoptosis and antagonizing urokinase plasminogen activator activity.
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Ethyl isopropyl amiloride inhibits smooth muscle cell proliferation and migration by inducing apoptosis and antagonizing urokinase plasminogen activator activity.

机译:异丙基阿米洛利乙酯通过诱导凋亡和拮抗尿激酶纤溶酶原激活剂的活性,抑制平滑肌细胞的增殖和迁移。

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摘要

Amiloride inhibits activation of the Na(+)-H+ exchanger (NHE), a critical step in smooth muscle cell (SMC) growth. While amiloride treatment reduces SMC proliferation and migration, as well as experimental lesion formation, these effects are not exclusively due to NHE inhibition and remain incompletely understood. The purpose of this study was to examine the mechanisms involved in amiloride-induced attenuation of SMC proliferation and migration, looking specifically at the potential role of apoptosis and urokinase plasminogen activator (uPA) activity in these processes. Rabbit SMCs in tissue culture were exposed to 10-80 microM of the amiloride analogue ethyl isopropyl amiloride (EIPA). Compared with controls, EIPA reduced DNA synthesis, cell number, and mitochondrial respiration, but without toxic effects on quiescent or proliferating cells. In a Boyden chamber assay, EIPA reduced uPA-induced SMC migration. Moreover, in a SMC scratch assay EIPA treatment resulted in a 66% reduction in the number of repopulating cells, a 92% decrease in the number of proliferating cells, and a 37-fold increase in the number of apoptotic cells. SMC apoptosis was frequently localized to the scratch edges, where cell proliferation and bcl-2 expression were absent. Finally, uPA enzymatic activity in the cell culture media was lower for EIPA-treated versus control SMCs. Therefore, EIPA inhibits both SMC proliferation and migration by inducing apoptosis and antagonizing uPA activity, respectively, and requires further study as an agent for reducing vascular lesion formation.
机译:阿米洛利抑制Na(+)-H +交换子(NHE)的激活,这是平滑肌细胞(SMC)生长的关键步骤。尽管阿米洛利治疗减少了SMC的增殖和迁移以及实验性病变的形成,但这些作用并非仅由于NHE抑制而仍未完全了解。这项研究的目的是检查与阿米洛利诱导的SMC增殖和迁移减弱有关的机制,特别是研究凋亡和尿激酶纤溶酶原激活剂(uPA)活性在这些过程中的潜在作用。将组织培养中的兔SMC暴露于10-80 microM的阿米洛利类似物乙基异丙基阿米洛利(EIPA)。与对照组相比,EIPA减少了DNA的合成,细胞数量和线粒体呼吸,但对静止或增生的细胞没有毒性作用。在博伊登室测定中,EIPA减少了uPA诱导的SMC迁移。此外,在SMC刮擦试验中,EIPA处理导致再增殖细胞数量减少66%,增殖细胞数量减少92%,凋亡细胞数量增加37倍。 SMC凋亡通常定位在没有细胞增殖和bcl-2表达的划痕边缘。最后,与对照SMC相比,EIPA处理的细胞培养基中的uPA酶活性较低。因此,EIPA分别通过诱导凋亡和拮抗uPA活性来抑制SMC增殖和迁移,并且作为减少血管病变形成的试剂需要进一步研究。

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