Chronic cathepsin inhibition by E-64 in Dahl salt-sensitive rats.
Chronic cathepsin inhibition by E-64 in Dahl salt-sensitive rats.
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DOI：
10.14814/phy2.12950
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发表时间：
2016-09
影响因子：
2.5
通讯作者：
Staruschenko A
中科院分区：
文献类型：
--
作者：
Blass G;Levchenko V;Ilatovskaya DV;Staruschenko A
半胱氨酸组织蛋白酶是在肾脏和其他组织中表达的溶酶体酶，参与细胞蛋白质的成熟和分解。它们已被证明与许多心血管和肾脏疾病的进展密切相关。本研究的目的是确定半胱氨酸组织蛋白酶在盐敏感性高血压和相关肾脏损害的发生中的作用。在我们的实验中，Dahl 盐敏感 (SS) 大鼠喂食 8% 高盐氯化钠饮食，并静脉注射不可逆半胱氨酸组织蛋白酶抑制剂 E-64（1 毫克/天）或载体（对照）。对照组和 E-64 输注组均出现显着的高血压和肾脏损伤，且两组之间的平均动脉压和高血压相关蛋白尿没有差异。接下来，我们使用共聚焦钙成像测试了对照组和输注组足细胞中的基础钙水平。各组之间的基础钙没有差异，表明组织蛋白酶抑制缺乏保护性或加重性影响。 E-64 的功效通过蛋白质印迹法进行了测试。我们的研究结果与之前报道的一致，E-64 诱导组织蛋白酶 B 和 L 丰度增加。我们的结论是，E-64 对半胱氨酸组织蛋白酶的抑制对血压发展和肾脏损伤没有任何影响，至少在 SS 高血压模型的研究条件下是这样。
Cysteine cathepsins are lysosomal enzymes expressed in the kidneys and other tissues, and are involved in the maturation and breakdown of cellular proteins. They have been shown to be integrally involved in the progression of many cardiovascular and renal diseases. The goal of this study was to determine the involvement of cysteine cathepsins in the development of salt‐sensitive hypertension and associated kidney damage. In our experiments, Dahl salt‐sensitive (SS) rats were fed an 8% high salt NaCl diet and intravenously infused with the irreversible cysteine cathepsin inhibitor E‐64 (1 mg/day) or the vehicle (control). Both the control and E‐64 infused groups developed significant hypertension and kidney damage, and no difference of the mean arterial pressure and the hypertension‐associated albuminuria was observed between the groups. We next tested basal calcium levels in the podocytes of both control and infused groups using confocal calcium imaging. Basal calcium did not differ between the groups, indicative of the lack of a protective or aggravating influence by the cathepsin inhibition. The efficacy of E‐64 was tested in Western blotting. Our findings corresponded to the previously reported, E‐64 induced increase in cathepsin B and L abundance. We conclude that the inhibition of cysteine cathepsins by E‐64 does not have any effects on the blood pressure development and kidney damage, at least under the studied conditions of this model of SS hypertension.