一氧化氮合酶的作用机制

一氧化氮合酶的作用机制赵慧卿（安徽医科大学化学教研室,合肥２３００３２）关键词一氧化氮一氧化氮合酶８０年代以来,人们发现一氧化氮在许多生理过程中起着十分重要的作用［１］。在血管内皮细胞中,一氧化氮可激活可溶性鸟苷酸环化酶（ｓＧＣ）,通过升高环鸟苷酸水...     

真菌中一氧化氮生物合成、降解及功能的研究进展

一氧化氮是一个有较高活性的自由基气体分子,无论在动植物还是微生物中,作为一个细胞内和细胞间的信号传导分子,它在许多的生理和病理过程中都发挥着双向的调节作用.研究发现真菌细胞可以合成一氧化氮,适当浓度的一氧化氮在真菌细胞内发挥多种重要的生物学功能,一旦一氧化氮过量累积,这个自由基分子会对细胞造成伤害,导致细胞凋亡.一氧化氮介导生成的环鸟苷酸(cGMP)作为一种重要的第二信使分子涉及到真菌细胞内多种信号途径的调控,调节了整个真菌类群的生长发育、形态发生、孢子形成和萌发、繁殖和细胞凋亡的过程,影响了真菌整个生命周期的生理活动.到目前为止,尽管一氧化氮在动植物中作用的机制得到了广泛的研究,但一氧化氮在真菌中的研究报道很有限.关于一氧化氮在真菌中的合成和降解途径,一氧化氮介导的信号传导机制的研究还不透彻,它在真菌细胞内的功能和毒理还有待于更深入的研究.     

神经型一氧化氮合酶的活性调控

一氧化氮是重要的信使分子,在生物体内参与众多生理及病理过程。生物体内存在着复杂的一氧化氮合酶活性调控机制以精确调控一氧化氮的生成。在神经系统中,一氧化氮主要由神经型一氧化氮合酶催化生成。神经型一氧化氮合酶的活性主要受到翻译后水平上钙离子和钙调蛋白的调控,其调控方式包括二聚化、多位点的磷酸化和去磷酸化,以及主要由PDZ结构域介导的蛋白质-蛋白质相互作用。一氧化氮本身对其合酶的活性具有负反馈调控作用。近年来的研究提示,细胞质膜上的脂筏微区在神经性一氧化氮合酶的活性调控中也起到重要的调节作用。     

一氧化氮的抗感染免疫作用及其机制

一氧化氮在机体抗感染免疫防御体系中的重要作用被发现之后,各国学者进行了大量的相关研究。这些研究证明：一氧化氮作为活化巨噬细胞的一种细胞毒效分子,在抑制和杀伤病毒,细菌,寄生虫等的免疫应答中起重要作用。一氧化氮抗感染的作用机制十分复杂,它通过调节Th1/Th2的平衡来促进机体的免疫应答,并可直接与含铁酶的Fe-S基团结合,破坏酶的活性,进而杀伤病原体及其宿主细胞。     

核因子κB、NO 与肺纤维化的研究进展

国内外对导致肺纤维化的肺部疾病中诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)基因在NF-κB参与诱导活化下,催化合成的一氧化氮(nitric oxide,NO)在肺纤维化过程中发挥细胞保护性及细胞毒性双重作用的研究已取得一些进展。本文主要阐述iNOS基因在NF-κB诱导活化下合成的NO与肺纤维化的关系,从而为NO作用的双重性和网络性及NO与肺纤维化关系的研究提供一些线索。     

软体动物的一氧化氮及其合酶的研究进展

一氧化氮作为一种重要的信息分子,参与调节软体动物的嗅觉、运动、取食、机体防御及学习行为。本文从生理、生化、形态定位以及信号转导几方面综述了有关软体动物一氧化氮及其合酶的最新研究进展。     

昆虫一氧化氮及其合酶的研究进展

一氧化氮作为一种重要的信息分子 ,参与调节昆虫嗅觉、视觉、机械感受、发育、机体防御及学习行为。该文从生理、生化、形态定位以及信号转导几方面综述了有关昆虫一氧化氮及其合酶的最新研究进展。     

一氧化氮合成酶分子生物学进展

一氧化氮合成酶分子生物学进展张登海（上海医科大学２０００３２）一氧化氮（ＮＯ）是一种重要的信使分子,它参与血管调节、神经传递、炎症、免疫反应等过程,在多种疾病的发病中有重要作用。在哺乳动物,ＮＯ的作用涉及几乎所有的脏器。ＮＯ由ＮＯ合成酶（ＮＯＳ）合成...     

一氧化氮、人乳头瘤病毒和宫颈癌之间相互关系的研究进展

人乳头瘤病毒感染是宫颈癌发生的重要始动原因,从HPV感染到宫颈癌发生,需要许多共刺激因子的参与。这些共刺激因子均可引起宫颈局部一氧化氮浓度的增高。而一氧化氮既可影响HPV的转录和翻译,又在肿瘤发生过程中具有重要调节作用。深入研究一氧化氮、人乳头瘤病毒感染及宫颈癌之间的关系,可为宫颈癌的防治提供新的重要理论基础和药物研制实验平台,通过使用一氧化氮合酶抑制剂降低宫颈局部NO浓度将为全面有效防治宫颈癌带来新的希望。     

一氧化氮与雄性生殖系统

一氧化氮是近年来发现的一种重要的生物信号分子和效应分子 ,在生物体内 ,L 精氨酸在一氧化氮合酶的作用下生成一氧化氮后 ,以自分泌或旁分泌形式作用于自身或邻近的细胞 ,发挥信号传导和细胞毒性等多种生理功能。近年来的研究表明 ,一氧化氮对雄性生殖系统上至下丘脑 ,下到性腺、附性器官都具有十分重要的生理调节作用。     

Therapeutic approaches using nitric oxide in infants and children

Pulmonary hypertension contributes significantly to the morbidity and mortality associated with many pediatric pulmonary and cardiac diseases. Nitric oxide, a gas molecule, is a unique pharmaceutical agent that can be inhaled and thus delivered directly to the lung. Inhaled nitric oxide was approved by the FDA in 1999 as a therapy for infants with persistent pulmonary hypertension. Since then, the use of inhaled nitric oxide has expanded to other neonatal and pediatric conditions, and our knowledge of its properties and mechanisms of action has increased tremendously. This review discusses the physiology of nitric oxide signaling, the most common indications for its clinical use, and promising new investigations that may enhance endogenous production of nitric oxide and/or improve vascular response to it.     

一氧化氮的功能及其作用机制(Ⅰ)——性质与功能

一氧化氮(nitric oxide,NO)是第一个被发现的参与细胞信号转导的气体信号分子。NO参与的生命活动非常广泛,在神经、免疫、呼吸等系统中发挥着重要作用。很久以来,一氧化氮合酶(nitric oxide synthase,NOS)被认为是人体内合成NO的主要途径,其活性受到严格的调控。直到最近,人们才发现亚硝酸盐(nitrite,NO2-)也可以参与体内NO的合成。本综述总结NO的相关性质与功能,并简介亚硝酸盐的研究进展。     

Ultrastructural localization of nitric oxide synthase and endothelin in coronary and pulmonary arteries of newborn rats

This is the first report on the ultrastructural distribution of nitric oxide synthase and endothelin immunoreactivities in the coronary and pulmonary arteries of newborn Wistar rats. The distribution of nitric oxide synthase and endothelin was investigated using pre-embedding peroxidase-antiperoxidase immunocytochemistry. In both arteries examined, positive labelling for nitric oxide synthase was localized both in the endothelium and smooth muscle, whereas positive labelling for endothelin was localized in the endothelium exclusively. In the coronary artery, approximately 80% and 55% of the endothelial cells examined were positive for nitric oxide synthase and endothelin, respectively, whereas in the pulmonary artery, 77% and 60% of the endothelial cells were positive for nitric oxide synthase and endothelin, respectively. These findings indicate that nitric oxide synthase and endothelin are colocalized in some of the endothelial cells of the newborn rat. In the endothelium, nitric oxide synthase and endothelin immunoreactivities were distributed throughout the cell cytoplasm and in association with the membranes of intracellular organelles. In smooth muscle, a relationship of nitric oxide synthase immunoreactivity to endoplasmic reticulum was observed in the pulmonary artery. In summary, in the newborn rat, endothelial cells of the coronary and pulmonary artery are rich in nitric oxide synthase (neuronal isoform) and endothelin, and it is suggested therefore that they may be substantially involved in vasomotor control of the cardiac and pulmonary circulation during early stages of postnatal development.     

Nitric oxide/cGMP protects endothelial cells from hypoxia-mediated leakiness

Leakiness of the endothelial bed is attributed to the over-perfusion of the pulmonary bed, which leads to high altitude pulmonary edema (HAPE). Inhalation of nitric oxide has been successfully employed to treat HAPE patients. We hypothesize that nitric oxide intervenes in the permeability of the pulmonary macrovascular endothelial bed to rectify the leaky bed under hypoxia. Our present work explores the underlying mechanism of 'hypoxia-mediated' endothelial malfunction by using human umbilical cord-derived immortalized endothelial cells, ECV-304, and bovine pulmonary artery primary endothelial cells. The leakiness of the endothelial monolayer was increased by two-fold under hypoxia in comparison to cells under normoxia, while optical tweezers-based tethering assays reported a higher membrane tension of endothelial cells under hypoxia. Phalloidin staining demonstrated depolymerization of F-actin stress fibers and highly polarized F-actin patterns in endothelial cells under hypoxia. Nitric oxide, 8-Br-cGMP and sildenafil citrate (phosphodiesterase type 5 inhibitor) led to recovery from hypoxia-induced leakiness of the endothelial monolayers. Results of the present study also suggest that 'hypoxia-induced' cytoskeletal rearrangements and membrane leakiness are associated with the low nitric oxide availability under hypoxia. We conclude that nitric oxide-based recovery of hypoxia-induced leakiness of endothelial cells is a cyclic guanosine monophosphate (cGMP)-dependent phenomenon.     

一氧化氮的功能及其作用机制(Ⅱ)——蛋白质巯基亚硝基化修饰

一氧化氮的功能多样,其作用机制也是复杂而相互关联的,是多靶点、多机制同时作用的调控网络。除了经典的cGMP依赖的信号通路外,一氧化氮还能通过对蛋白质的半胱氨酸巯基进行蛋白质翻译后修饰而起作用。蛋白质巯基亚硝基化修饰(protein S-nitrosation)是活性氮对蛋白质半胱氨酸巯基的一种蛋白质翻译后修饰,在一氧化氮的作用机制中占有重要位置。本综述简要总结蛋白质巯基亚硝基化修饰的功能及作用机制。     

Detection of nitrous oxide in the neuronal nitric oxide synthase reaction by gas chromatography-mass spectrometry

Using headspace gas chromatography-mass spectrometry, we detected significant amounts of nitrous oxide in the reaction products of the monooxygenase reaction catalyzed by neuronal nitric oxide synthase. Nitrous oxide is a dimerization product of nitroxyl anion; its presence in the reaction products indicates that the nitroxyl anion is a product of the neuronal nitric oxide synthase-catalyzed reaction.     

{Different Signalling Pathways Mediate the Opposite Effects of Endogenous Versus Exogenous Nitric Oxide on Hydroperoxide Toxicity in CHP100 neuroblastoma Cells

The results presented in this study indicate that the toxic response brought about by increasing concentrations of tert-butylhydroperoxide in CHP100 cells was mitigated significantly by exogenously added nitric oxide donors via a cyclic GMP-independent mechanism. In contrast with these results, endogenous nitric oxide generated by the Ca2+-mobilizing agent caffeine was found to increase hydroperoxide toxicity. Under these conditions, nitric oxide was not directly toxic to the cells. Rather, nitric oxide was found to promote the caffeine-mediated release of Ca2+ from ryanodine-sensitive Ca2+ stores via a cyclic GMP-independent mechanism. Release of the cation from ryanodine-sensitive Ca2+ stores was causally linked with the caffeine/nitric oxide-mediated enhancement of tert-butylhydroperoxide toxicity. It is concluded that endogenous and exogenous nitric oxide activate diverging signalling pathways independent of cyclic GMP formation and causing opposite effects on the toxic response evoked by tert-butylhydroperoxide in CHP100 cells.     

Malignant glioma progression and nitric oxide

Glioblastoma multiforme, the most common of the malignant gliomas, carries a dismal prognosis in spite of the most aggressive therapy and recent advances in molecular pathways of glioma progression. Although it has received relatively little attention in the setting of malignant gliomas, nitric oxide metabolism may be intimately associated with the disease process. Interestingly, nitric oxide has both physiological roles (e.g., neurotransmitter-like activity, stimulation of cyclic GMP), and pathophysiological roles (e.g., neoplastic transformation, tumor neovascularization, induction of apoptosis, free radical damage). Moreover, whether nitric oxide is neuroprotective or neurotoxic in a given disease state, or whether it enhances or diminishes chemotherapeutic efficacy in malignant neoplasia, is unresolved. This review discusses the multifaceted activity of nitric oxide with particular reference to malignant gliomas.