Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland.
Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland.
Pharmacol Res. 2018 Mar;129:56-64. doi: 10.1016/j.phrs.2018.01.008. Epub 2018 Jan 31.
Heme oxygenase (HO) catalyzes the degradation of toxic free heme to the equimolar amounts of biliverdin, Fe and concurrently releases of carbon monoxide (CO). CO is nowadays increasingly recognized as an important signaling molecule throughout the body that is involved in many physiological processes and shows multidirectional biological activity. Recent evidence indicates that CO exhibits the anti-inflammatory, anti-proliferative, anti-apoptotic, anti-aggregatory and vasodilatory properties. The cellular mechanisms underlying the activity of CO involve stimulation of cGMP-dependent signaling pathway and large conductance calcium activated K channels, the activation of mitogen-activated protein kinases and the nuclear factor k-light chain-enhancer of activated B cells transcription factor pathway. Stimulation of endogenous CO production by HO inducers or the inhalation of CO or the delivery of this gaseous molecule by novel pharmaceutical agents have been found in experimental animal models to be promising in the future therapy of various diseases. CO appears to act as a significant component of the complex mechanism of gastrointestinal (GI) mucosal defense. This gaseous molecule plays an important role in diabetic gastroparesis, prevention of the upper GI mucosal damage, post-operative ileus and the healing of ulcerative colitis. This review focuses on the better understanding mechanisms through which CO contributes to the mechanism of protection, resistance to injury and ulcer healing. It is becoming apparent that the pleiotropic effect of this molecule may increase clinical applicability of CO donors and their implementation in many pharmacological research areas, pharmaceutical industry and health-care system.
血红素加氧酶（HO）催化有毒游离血红素降解为等摩尔量的胆红素、Fe，并同时释放一氧化碳（CO）。CO 如今被越来越多地认为是全身重要的信号分子，参与许多生理过程并表现出多向生物活性。最近的证据表明，CO 具有抗炎、抗增殖、抗凋亡、抗聚集和血管舒张作用。CO 活性的细胞机制涉及刺激 cGMP 依赖性信号通路和大电导钙激活的 K 通道、丝裂原激活的蛋白激酶和核因子 k-轻链增强子激活的 B 细胞转录因子途径的激活。在实验动物模型中发现，HO 诱导剂刺激内源性 CO 产生、吸入 CO 或通过新型药物制剂输送这种气态分子，有望成为未来治疗各种疾病的方法。CO 似乎是胃肠道（GI）黏膜防御复杂机制的重要组成部分。这种气态分子在糖尿病性胃轻瘫、预防上 GI 黏膜损伤、术后肠梗阻和溃疡性结肠炎的愈合中发挥重要作用。本文综述了更好地理解 CO 有助于保护、抵抗损伤和溃疡愈合机制的相关机制。显然，这种分子的多效性可能会增加 CO 供体的临床适用性，并将其应用于许多药理学研究领域、制药行业和医疗保健系统。
