Influence of Angiotensin II on cell viability and apoptosis in rat renal proximal tubular epithelial cells in in vitro studies.

IF 2.1 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Journal of the Renin-Angiotensin-Aldosterone System Pub Date : 2020-07-01 DOI:10.1177/1470320320949850
Aleksandra Piotrowska, Magdalena Chmielewska, Waldemar Andrzejewski, Piotr Dziegiel, Marzenna Podhorska-Okolow
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引用次数: 1

Abstract

Introduction: Angiotensin II (Ang II) is multifunctional peptide that plays an important role in blood pressure regulation and maintenance electrolyte homeostasis. It shows biological effects by activating two main receptors: AT1 and AT2. The aim of the present work was to investigate the effect of Ang II on NRK-52E cells in in vitro studies. Furthermore, an attempt was made to determine the effectiveness of the AT1 and AT2 receptor blocker activity (respectively, losartan and PD123319).

Methods: The study was carried out using adherent NRK-52E cell line. Immunofluorescence and Western Blot method were used to confirm the presence of AT1 and AT2 receptors in the cells. The SRB and MTT tests showed decrease in the viability of NRK-52E cells incubated with Ang II in comparison to the control (without Ang II).

Results: The blockade of the AT1 receptor caused an increase in cell viability in comparison to cells incubated with Ang II only. The blockade of AT2 receptor also triggered statistically significant increase in cell viability in comparison with cells only exposed to Ang II. Combined administration of blockers for both receptors (losartan and PD123319) decreased Ang II cytotoxicity against NRK-52E cell line. The apoptosis was only observed in cells incubated with Ang II in comparison with control cells. However, simultaneous use of both blockers caused statistically significant decrease in apoptosis.

Conclusions: The result of our study indicates that Ang II causes damaging effect on NRK-52E cells by directing them to programmed cell death. It seems that not only does the AT2 receptor itself play an important role in the induction of apoptosis, but also its interaction with AT1 receptor does as well.

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血管紧张素II对大鼠肾近端小管上皮细胞活力和凋亡影响的体外研究
血管紧张素II (Angiotensin II, Ang II)是一种多功能肽,在调节血压和维持电解质稳态中起重要作用。它通过激活两个主要受体AT1和AT2来显示生物学效应。本研究的目的是在体外研究Ang II对NRK-52E细胞的影响。此外,还尝试确定AT1和AT2受体阻滞剂活性的有效性(分别为氯沙坦和PD123319)。方法:采用NRK-52E贴壁细胞系进行研究。免疫荧光法和Western Blot法证实细胞中存在AT1和AT2受体。SRB和MTT试验显示,与对照(不含Ang II)相比,与Ang II孵育的NRK-52E细胞的活力下降。结果:与仅与Ang II孵育的细胞相比,AT1受体的阻断导致细胞活力增加。与仅暴露于Ang II的细胞相比,AT2受体的阻断也触发了统计学上显著的细胞活力增加。联合使用两种受体(氯沙坦和PD123319)阻滞剂可降低Ang II对NRK-52E细胞系的细胞毒性。与对照细胞相比,仅在与Ang II孵育的细胞中观察到细胞凋亡。然而,同时使用两种阻滞剂导致细胞凋亡显著减少。结论:我们的研究结果表明,Ang II通过引导NRK-52E细胞程序性死亡而对其产生损伤作用。似乎不仅AT2受体本身在诱导细胞凋亡中起重要作用,其与AT1受体的相互作用也起重要作用。
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来源期刊
CiteScore
6.20
自引率
0.00%
发文量
16
审稿时长
6-12 weeks
期刊介绍: JRAAS is a peer-reviewed, open access journal, serving as a resource for biomedical professionals, primarily with an active interest in the renin-angiotensin-aldosterone system in humans and other mammals. It publishes original research and reviews on the normal and abnormal function of this system and its pharmacology and therapeutics, mostly in a cardiovascular context but including research in all areas where this system is present, including the brain, lungs and gastro-intestinal tract.
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