Myocardial Infarction Research Laboratory, Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Antioxid Redox Signal. 2020 Dec 20;33(18):1332-1349. doi: 10.1089/ars.2020.8171.
Sulfide was revealed to be an endogenous signaling molecule regulating a plethora of cellular functions. It is involved in the regulation of fundamental processes, including blood pressure regulation, suspended animation, and metabolic activity of mitochondria, pain, and inflammation. The underlying biochemical pathways and pharmacological targets are still largely unidentified. Red blood cells (RBCs) are known as oxygen transporters and were proposed to contribute to cardiovascular homeostasis by regulating nitric oxide (NO) metabolism, also interaction of hemoglobin with nitrite and NO itself. Interestingly, recent evidence indicates that RBCs may also play a central role in systemic sulfide metabolism and homeostasis, and, potentially, in the crosstalk with NO. Heme-containing proteins such as hemoglobin were shown to be targeted by both NO and sulfide. In this article, we aim at revising and discussing the potential impact of RBCs on systemic sulfide metabolism in the cardiovascular system. Although the synthetic pathways and the reactivity of hemoglobin and other heme proteins with sulfide and NO are known, the role of RBCs in sulfide metabolism, physiology, pharmacology, and its pathophysiological implications have not been characterized so far. To allow a better understanding of the role of RBCs in systemic sulfide metabolism and its cross-talk with NO, basic and translational science studies should be focused on dissecting the enzymatic and nonenzymatic sulfur metabolic pathways in RBCs and their impact on the cardiovascular system in animal models and clinical settings.
硫化物被揭示为一种内源性信号分子，调节多种细胞功能。它参与调节基本过程，包括血压调节、悬浮生物和线粒体代谢活性、疼痛和炎症。其潜在的生化途径和药理学靶点在很大程度上仍未被确定。红细胞（RBC）是众所周知的氧气转运体，据推测通过调节一氧化氮（NO）代谢来促进心血管稳态，血红蛋白与亚硝酸盐和 NO 本身的相互作用也是如此。有趣的是，最近的证据表明，红细胞可能在全身硫化物代谢和稳态中也发挥核心作用，并可能与 NO 相互作用。含血红素的蛋白质，如血红蛋白，被证明是同时受到 NO 和硫化物的靶向作用。在本文中，我们旨在修订和讨论 RBC 在心血管系统中对全身硫化物代谢的潜在影响。虽然已经知道血红蛋白和其他血红素蛋白与硫化物和 NO 的合成途径和反应性，但到目前为止，尚未对 RBC 在硫化物代谢、生理学、药理学及其病理生理学意义中的作用进行特征描述。为了更好地理解 RBC 在全身硫化物代谢及其与 NO 的相互作用中的作用，应该侧重于基础和转化科学研究，以剖析 RBC 中的酶和非酶硫代谢途径及其对动物模型和临床环境中心血管系统的影响。
