Effects of chronic renal failure on caveolin-1, guanylate cyclase and AKT protein expression.
Effects of chronic renal failure on caveolin-1, guanylate cyclase and AKT protein expression.
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DOI：
10.1016/j.bbadis.2004.06.013
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发表时间：
2004-11
期刊：
影响因子：
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通讯作者：
R. Sindhu;A. Ehdaie;N. Vaziri;C. Roberts
中科院分区：
文献类型：
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作者：
R. Sindhu;A. Ehdaie;N. Vaziri;C. Roberts
慢性肾功能衰竭（CRF）已被证明会导致氧化应激和改变一氧化氮（NO）代谢。然而，CRF对NO生物活性相关蛋白的影响尚未研究。本研究旨在验证CRF会诱导小窝蛋白-1（Cav-1）、可溶性鸟苷酸环化酶（sGC）和Akt（这三种蛋白在调节一氧化氮合酶（NOS）功能中起重要作用）变化的假设。雄性Sprague-Dawley大鼠通过5/6肾切除术或假手术对照组随机分配至CRF组。6周后，测定两组大鼠的体重、血压、肌酐清除率、血浆肌酐、尿环磷酸鸟苷（cGMP）以及肾脏、主动脉、心脏和肝脏组织中Cav-1、sGC和Akt的免疫检测水平。慢性肾衰竭导致体重和肌酸酐清除率明显下降，血压和血浆肌酸酐升高。观察到肾组织中sGC蛋白丰度明显上调，而主动脉、心脏和肝脏中无变化。这伴随着尿cGMP水平的降低，表明sGC功能障碍。主动脉、肝、肾组织中Cav-1蛋白丰度增加。相反，CRF抑制主动脉、心脏和肝脏组织中Akt的丰度。这些数据证明，CRF的特征在于调节肝、血管、心脏和肾组织中NO功能的蛋白质丰度的改变，以及cGMP的减少，这有助于高血压和先前在该模型中注意到的NO生物活性的变化。
Chronic renal failure (CRF) has been documented to cause oxidative stress and alter nitric oxide (NO) metabolism. However, the effect of CRF on proteins related to NO bioactivity has not been investigated. The present study was designed to test the hypothesis that CRF would induce changes in caveolin-1 (Cav-1), soluble guanylate cyclase (sGC) and Akt, three proteins important in regulating NO synthase (NOS) functionality. Male Sprague–Dawley rats were randomized to CRF via 5/6 nephrectomy or sham-operated control groups. After 6 weeks, body weight, blood pressure, creatinine clearance, plasma creatinine, urinary cyclic guanosine monophosphate (cGMP) and immunodetectable levels of Cav-1, sGC and Akt were determined in the renal, aorta, heart and liver tissues from both groups. CRF resulted in marked decreases in body weight and creatinine clearance, and elevation of blood pressure and plasma creatinine. An apparent upregulation of sGC protein abundance in renal tissue was noted, with no change in aorta, heart and liver. This was accompanied by a reduction in urinary cGMP levels, indicative of sGC dysfunction. Cav-1 protein abundance was increased in aortic, liver and renal tissues. In contrast, CRF depressed Akt abundance in aorta, heart and liver tissues. These data document that CRF is characterized by alteration in the abundance of proteins regulating NO function in hepatic, vascular, cardiac and renal tissues, and a decrease in cGMP, which contributes to hypertension and changes in NO bioactivity previously noted in this model.