Chair of Pharmacology, Section of Medicine, University of Fribourg, Switzerland.
FEBS J. 2022 May;289(9):2481-2515. doi: 10.1111/febs.16135. Epub 2021 Aug 5.
Cyanide is traditionally viewed as a cytotoxic agent, with its primary mode of action being the inhibition of mitochondrial Complex IV (cytochrome c oxidase). However, recent studies demonstrate that the effect of cyanide on Complex IV in various mammalian cells is biphasic: in lower concentrations (nanomolar to low micromolar) cyanide stimulates Complex IV activity, increases ATP production and accelerates cell proliferation, while at higher concentrations (high micromolar to low millimolar) it produces the previously known ('classic') toxic effects. The first part of the article describes the cytotoxic actions of cyanide in the context of environmental toxicology, and highlights pathophysiological conditions (e.g., cystic fibrosis with Pseudomonas colonization) where bacterially produced cyanide exerts deleterious effects to the host. The second part of the article summarizes the mammalian sources of cyanide production and overviews the emerging concept that mammalian cells may produce cyanide, in low concentrations, to serve biological regulatory roles. Cyanide fulfills many of the general criteria as a 'classical' mammalian gasotransmitter and shares some common features with the current members of this class: nitric oxide, carbon monoxide, and hydrogen sulfide.
氰化物传统上被视为细胞毒性剂，其主要作用模式是抑制线粒体复合物 IV（细胞色素 c 氧化酶）。然而，最近的研究表明，氰化物对各种哺乳动物细胞中复合物 IV 的作用是双相的：在较低浓度（纳摩尔到低微摩尔）下，氰化物刺激复合物 IV 活性，增加 ATP 产生并加速细胞增殖，而在较高浓度（高微摩尔到低毫摩尔）下，它会产生先前已知的（“经典”）毒性作用。本文的第一部分描述了氰化物在环境毒理学背景下的细胞毒性作用，并强调了病理生理条件（例如，假单胞菌定植的囊性纤维化），其中细菌产生的氰化物对宿主产生有害影响。本文的第二部分总结了哺乳动物氰化物产生的来源，并概述了一个新兴概念，即哺乳动物细胞可能以低浓度产生氰化物，以发挥生物调节作用。氰化物符合许多作为“经典”哺乳动物气体递质的一般标准，并与该类别的当前成员具有一些共同特征：一氧化氮、一氧化碳和硫化氢。
