Dose Response of Bumetanide on Aquaporins and Angiogenesis Biomarkers in Human Retinal Endothelial Cells Exposed to Intermittent Hypoxia.
Dose Response of Bumetanide on Aquaporins and Angiogenesis Biomarkers in Human Retinal Endothelial Cells Exposed to Intermittent Hypoxia.
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布美他尼对暴露于间歇性缺氧的人视网膜内皮细胞中水通道蛋白和血管生成生物标志物的剂量反应。
DOI：
10.3390/ph14100967
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发表时间：
2021-09-24
期刊：
影响因子：
--
通讯作者：
Beharry KD
中科院分区：
文献类型：
--
作者：
Guzel S;Cai CL;Aranda JV;Beharry KD
水通道蛋白（AQPs）在调节细胞水分、溶质运输和平衡方面具有重要作用。近年来，AQPs也被认为在细胞迁移和血管生成中起着关键作用。在视网膜中，缺氧诱导血管内皮生长因子（VEGF），这是一种有效的血管生成和血管通透性因子，导致视网膜水肿，这是由aqp促进的。布美他尼是一种利尿剂和aqp1 - 4阻滞剂。我们验证了布美他尼抑制AQPs改善间歇性缺氧（IH）诱导的人微血管视网膜内皮细胞（HMRECs）血管生成和氧化应激的假设。用低剂量（0.05µg/mL）或高剂量（0.2µg/mL）布美他尼处理HMRECs，并暴露于低氧（Nx）、高氧（50% O2）或IH (50% O2，短暂缺氧5% O2) 24,48和72小时。在培养基中测定血管生成和氧化应激生物标志物，并评估细胞的管形成能力和AQP-1和-4表达。两种剂量的布美他尼均可显著降低氧化应激和血管生成生物标志物。这种反应反映在管的形成能力和AQP表达的减少上。这些发现证实了AQPs在视网膜血管生成中的作用。用布美他尼靶向aqp治疗可能有利于ih诱导的视网膜异常发育。
Aquaporins (AQPs) are important for regulating cellular water, solute transport, and balance. Recently, AQPs have also been recognized as playing a key role in cell migration and angiogenesis. In the retina, hypoxia induces vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, resulting in retinal edema, which is facilitated by AQPs. Bumetanide is a diuretic agent and AQP 1–4 blocker. We tested the hypothesis that bumetanide suppression of AQPs ameliorates intermittent hypoxia (IH)-induced angiogenesis and oxidative stress in human microvascular retinal endothelial cells (HMRECs). HMRECs were treated with a low-dose (0.05 µg/mL) or high-dose (0.2 µg/mL) of bumetanide and were exposed to normoxia (Nx), hyperoxia (50% O2), or IH (50% O2 with brief hypoxia 5% O2) for 24, 48, and 72 h. Angiogenesis and oxidative stress biomarkers were determined in the culture media, and the cells were assessed for tube formation capacity and AQP-1 and -4 expression. Both doses of bumetanide significantly decreased oxidative stress and angiogenesis biomarkers. This response was reflected by reductions in tube formation capacity and AQP expression. These findings confirm the role of AQPs in retinal angiogenesis. Therapeutic targeting of AQPs with bumetanide may be advantageous for IH-induced aberrant retinal development.
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影响因子：
3.6
作者：
Di Fiore, Juliann M.;Kaffashi, Farhad;Loparo, Kenneth;Sattar, Abdus;Schluchter, Mark;Foglyano, Ryan;Martin, Richard J.;Wilson, Christopher G.
通讯作者：
Wilson, Christopher G.
影响因子：
2.3
作者：
Di Fiore, Juliann M.;Vento, Maximo
通讯作者：
Vento, Maximo
影响因子：
5.1
作者：
Di Fiore, Juliann M.;Bloom, Jeffrey N.;Martin, Richard J.
通讯作者：
Martin, Richard J.
影响因子：
9.8
作者：
Chen, Jing;Smith, Lois E. H.
通讯作者：
Smith, Lois E. H.
DOI：
10.1186/s13046-016-0310-6
发表时间：
2016-02-24
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Dorward HS;Du A;Bruhn MA;Wrin J;Pei JV;Evdokiou A;Price TJ;Yool AJ;Hardingham JE
通讯作者：
Hardingham JE