Laboratory of Physiology, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy.
Statistical Unit, Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy.
Int J Mol Sci. 2024 Sep 25;25(19):10296. doi: 10.3390/ijms251910296.
Chromogranin B (CgB) is involved in the control of the cardiovascular system through the regulation of catecholamine release. Whether CgB can exert direct actions on the endothelium has not yet been clarified. Here, we aimed to investigate the effects of CgB on cell viability, mitochondrial membrane potential, reactive oxygen species (ROS), glutathione (GSH), nitric oxide (NO) release, and the cytosolic calcium concentration ([Ca]c) in human vascular endothelial cells (HUVECs) cultured under both physiological and peroxidative conditions. In HUVECs, experiments were conducted to establish the proper concentration and timing of CgB stimulation. Thereafter, specific assays were used to evaluate the response of HUVECs cultured in physiologic or oxidative stress conditions to CgB in the presence or absence of β-adrenergic receptor agonists and antagonists and intracellular pathways blockers. Analysis of cell viability, mitochondrial membrane potential, and NO release revealed that CgB was able to cause increased effects in HUVECs cultured in physiological conditions. Additionally, the same analyses performed in HUVECs cultured with HO, showed protective effects exerted by CgB, which was also able to counteract ROS release and maintain GSH levels. Furthermore, CgB played a dual role on the [Ca]c depending on the physiological or peroxidative cell culturing conditions. In conclusion, our data provide new information about the direct role of CgB in the physiological regulation of endothelial function and highlight its potential as a protective agent against peroxidative conditions, such as those found in cardiovascular diseases.
嗜铬粒蛋白 B(CgB)通过调节儿茶酚胺的释放参与心血管系统的控制。CgB 是否可以直接作用于内皮细胞尚未阐明。在这里,我们旨在研究 CgB 对培养在生理和过氧化条件下的人血管内皮细胞(HUVEC)的细胞活力、线粒体膜电位、活性氧(ROS)、谷胱甘肽(GSH)、一氧化氮(NO)释放和细胞质钙离子浓度 ([Ca]c) 的影响。在 HUVEC 中,进行实验以确定 CgB 刺激的适当浓度和时间。此后,使用特定的测定法来评估在生理或氧化应激条件下培养的 HUVEC 对 CgB 的反应,同时存在或不存在β-肾上腺素能受体激动剂和拮抗剂以及细胞内途径阻滞剂。细胞活力、线粒体膜电位和 NO 释放分析表明,CgB 能够在培养在生理条件下的 HUVEC 中引起增强的作用。此外,在培养有 HO 的 HUVEC 中进行的相同分析显示出 CgB 发挥的保护作用,它还能够抵抗 ROS 释放并维持 GSH 水平。此外,CgB 根据生理或过氧化细胞培养条件发挥双重作用对 [Ca]c。总之,我们的数据提供了关于 CgB 在血管内皮功能的生理调节中直接作用的新信息,并强调了其作为对抗心血管疾病等过氧化条件的保护剂的潜力。