Human recombinant leptin-induced nitric oxide release from endothelium depends on the membrane localization pattern of endothelial nitric oxide synthase

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-08-12 DOI:10.1016/j.tice.2025.103083

Reji Manjunathan , Swaraj Sinha , Akila Swaminathan , Dharanibalan Kasiviswanathan , Malathi Ragunathan , Suvro Chatterjee

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引用次数: 0

Abstract

The form of nitric oxide (NO) released from endothelial nitric oxide synthase (eNOS) can influence various aspects of the angiogenic process. The endogenous hormone leptin can induce different physiological processes, such as angiogenesis, at low concentrations. Several studies suggest that leptin's ability to induce endothelium-dependent vascular relaxation is mediated by stimulating NO through distinct signalling pathways. Therefore, an attempt has been made to understand the optimal concentration and incubation time of human recombinant leptin for the enzymatic release of NO from eNOS. Changes in the localisation and phosphorylation pattern of eNOS in cultured endothelium under different concentrations and incubation times are examined. Five nanomolar concentration of human recombinant leptin, within 6 min of incubation, can induce a significant level of NO from activated eNOS in cultured endothelium through plasma membrane localisation and phosphorylation of eNOS. Our findings suggest that human recombinant leptin can modulate NO-dependent pathways, opening new therapeutic avenues for angiogenesis-related disorders, such as wound healing, when used at appropriate concentrations and incubation times. This capacity of human recombinant leptin supports its potential therapeutic application in pathological conditions like ischaemic heart diseases and wound healing processes, where angiogenesis requires early intervention.

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重组瘦素诱导的一氧化氮从内皮细胞释放取决于内皮一氧化氮合酶的膜定位模式

内皮型一氧化氮合酶（eNOS）释放的一氧化氮（NO）的形式可以影响血管生成过程的各个方面。内源性激素瘦素在低浓度下可诱导不同的生理过程，如血管生成。一些研究表明，瘦素诱导内皮依赖性血管松弛的能力是通过不同的信号通路刺激NO介导的。因此，我们试图了解人重组瘦素在eNOS酶促释放NO的最佳浓度和孵育时间。研究了不同浓度和孵育时间培养内皮细胞中eNOS的定位和磷酸化模式的变化。5纳摩尔浓度的人重组瘦素，在6 min的孵育时间内，可通过eNOS的质膜定位和磷酸化，诱导培养内皮细胞中活化的eNOS产生显著水平的NO。我们的研究结果表明，在适当的浓度和孵育时间下，人重组瘦素可以调节no依赖途径，为血管生成相关疾病（如伤口愈合）开辟新的治疗途径。人重组瘦素的这种能力支持其在缺血性心脏病和伤口愈合过程等病理条件下的潜在治疗应用，在这些条件下血管生成需要早期干预。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.