Department of Bioscience, Aarhus University, Aarhus, Denmark.
Antioxid Redox Signal. 2020 Feb 1;32(4):258-265. doi: 10.1089/ars.2019.7877. Epub 2019 Oct 14.
Along with other gasotransmitters nitric oxide (NO) and carbon monoxide, hydrogen sulfide (HS) has recently emerged as an important signaling molecule with a particularly complex metabolism. Endogenous HS reacts with multiple cellular targets, including protein ferric heme groups, to elicit physiological responses, such as regulation of local blood flow. Recent evidence suggests that HS at low physiological concentrations is carried in the blood as bound to the small fraction of oxidized ferric hemoglobin (metHb). A relatively stable metHb-sulfide complex forms when HS and purified metHb react , with an affinity within the physiological range of sulfide in the blood. Formation and subsequent redox metabolism of metHb-sulfide complex have also been confirmed in isolated intact red blood cells (RBCs) containing enhanced metHb levels. Thus, HS may function as an endocrine signaling molecule and elicit responses at sites away from the site of production. In addition, metHb, considered as an inert or pathological hemoglobin derivative, may have a novel potential physiological role in the transport of HS in the blood. The transport of HS in the blood mediated by metHb would represent an O-independent pH-dependent mechanism for the blood-mediated control of blood flow and as such it is critical to understand the significance of this transport. Major challenges must be resolved to understand how metHb may carry HS in the RBCs, in particular determination of metHb-sulfide levels in the blood and identification of targets in the vasculature.
与其他气体递质一氧化氮 (NO) 和一氧化碳一样，硫化氢 (HS) 最近也成为一种重要的信号分子，其代谢过程特别复杂。内源性 HS 与多种细胞靶标（包括蛋白质三价铁血红素基团）反应，引起生理反应，如局部血流的调节。最近的证据表明，在低生理浓度下，HS 作为与一小部分氧化的三价血红蛋白（高铁血红蛋白，metHb）结合的形式存在于血液中。当 HS 与纯化的 metHb 反应时，会形成相对稳定的 metHb-硫复合物，其亲和力在血液中硫化物的生理范围内。在含有高铁血红蛋白水平增强的分离完整红细胞 (RBC) 中，也已经证实了 metHb-硫复合物的形成和随后的氧化还原代谢。因此，HS 可能作为一种内分泌信号分子，在远离产生部位的部位引发反应。此外，metHb 被认为是一种惰性或病理性的血红蛋白衍生物，它在血液中运输 HS 方面可能具有新的潜在生理作用。由 metHb 介导的 HS 在血液中的运输将代表一种 O2 独立的 pH 依赖机制，用于血液介导的对血流的控制，因此理解这种运输的意义至关重要。为了了解 metHb 如何在 RBCs 中携带 HS，必须解决重大挑战，特别是确定血液中 metHb-硫复合物的水平，并确定血管中的靶标。
